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333
Table 15.1 FDA-approved peptide drugs 2000–2022.
Peptide therapeutic
Approval
year
Method of
development
Target pharmacological
action Indication
Cetrorelix 2000 Synthetic Gonadotropin-releasing
hormone antagonist
Infertility
Bivalirudin 2000 Synthetic Inhibitor of prothrombin Anticoagulant
Caspofungin 2001 Semi-synthetic Cell wall synthesis
inhibitor
Aspergillosis
Nesiritide 2001 Recombinant
DNA technique
Atrial natriuretic
peptide-1 agonist
Chronic heart failure
Teriparatide 2002 Recombinant
DNA technique
Analog of parathyroid
hormone
Osteoporosis
Enfuvirtide 2003 Synthetic gp41 protein fusion
inhibitor of HIV-1 virus
HIV infections
Abarelix 2003 Synthetic Gonadotropin-releasing
hormone antagonist
Prostate cancer
Desirudin 2003 Recombinant
DNA technique
Inhibitor of human
thrombin
Prophylaxis of deep
thrombosis
Atazanavir 2003 Synthetic HIV-1 viral protease
inhibitor
HIV infections
Ziconotide 2004 Natural peptide
from the venom
of Conus magus
Blocks calcium channels Acute and chronic pain
Human secretin 2004 Synthetic Agonist for secretin
receptor
Pancreatic exocrine
dysfunction
Pramlintide 2005 Synthetic Agonist for calcitonin
receptor
Types 1 and 2 diabetes
mellitus
Micafungin 2005 Semi-synthetic Fungal cell wall synthesis
inhibitor
Candidiasis
Exenatide 2005 Synthetic GLP-1 agonist Type 2 diabetes
Lanreotide 2007 Synthetic Somatostatin receptor
agonist
Acromegaly
Romiplostim 2008 Phage display
technique
Thrombopoietin receptor
agonist
Thrombocytopenia
purpura
Romidepsin 2009 Natural, from
Chromobacterium
violaceum
Inhibitor of histone
deacetylase
Lymphoma of skin
Liraglutide 2010 Recombinant
DNA technique
GLP-1 agonist Type 2 diabetes and
obesity
Tesamorelin 2010 Synthetic Growth hormone-
releasing hormone agonist
Lipodystrophy
Telaprevir 2011 Synthetic NS3/4A viral protease
inhibitor
Hepatitis C
Boceprevir 2011 Synthetic NS3/4A viral protease
inhibitor
Hepatitis C
Icatibant 2011 Synthetic Bradykinin B2 receptor
antagonist
Genetic angioedema
(Continued)
334
Table 15.1 (Continued)
Peptide therapeutic
Approval
year
Method of
development
Target pharmacological
action Indication
Carfilzomib 2012 Semi-synthetic Proteasome inhibitor Multiple myeloma
Lucinactant 2012 Synthetic Reduce surface tension of
alveolar epithelium and
allow gas exchange
Respiratory distress
syndrome (RDS) in
premature infants
Pasireotide 2012 mRNA display Somatostatin receptors
agonist
Acromegaly
Peginesatide 2012 Synthetic Erythropoietin receptor
stimulant
For anemia in chronic
kidney disease (CKD)
patients on dialysis
Linaclotide 2012 Synthetic Guanylate cyclase-C
agonist
Irritable Bowel
Syndrome with
constipation (IBS-C) and
chronic idiopathic
constipation (CIC)
Teduglutide
2012 rDNA technology GLP-2 agonist Short bowel syndrome
Vasopressin 2014 Synthetic Vasopressin V2 receptor
agonist
Postoperative abdominal
distention, in abdominal
roentgenography to
dispel interfering gas
shadows, and in diabetes
insipidus
Dalbavancin 2014 Semi-synthetic
Bacterial cell wall
synthesis inhibitor
Antibacterial for acute
bacterial skin and skin
structure infection
(ABSSSI)
Oritavancin 2014 Semi-synthetic Inhibit transglycosylation Acute bacterial skin and
skin structure
Albiglutide 2014 rDNA technology GLP-1 agonist Type 2 diabetes
Dulaglutide 2014 rDNA technology GLP-1 agonist Type 2 diabetes
Parathyroid
hormone
2015 rDNA technology Parathyroid hormone 2
(PTH 2) receptor agonist
Hypocalcemia in
patients with
hypoparathyroidism
Lixisenatide 2016 rDNA technology GLP-1 receptor agonist Type 2 diabetes
Grazoprevir 2016 Synthetic NS3/4A viral protease
inhibitor
Hepatitis C virus in
combination with
elbasvir
Gallium dotatate
Ga-68
2016 Synthetic Binds to somatostatin
receptors
Diagnosis of
somatostatin receptor-
positive neuroendocrine
tumors (NETs)
Macimorelin 2017 Synthetic Growth hormone
secretagogue receptor type
1 agonist, increases
growth hormone secretion
Diagnosis of growth
hormone deficiency
Voxilaprevir 2017 Synthetic NS3/4A viral protease
inhibitor
Hepatitis C virus
335
Table 15.1 (Continued)
Peptide therapeutic
Approval
year
Method of
development
Target pharmacological
action Indication
Angiotensin II 2017 Synthetic Type-1 angiotensin II
receptor agonist
Increases blood pressure
in adults with septic or
other distributive shock
Plecanatide 2017 Synthetic Guanylate cyclase soluble
subunit alpha-2 agonist
CIC and IBS-C
Etelcalcetide
2017 Synthetic Calcium sensing receptor
agonist
Secondary
hyperparathyroidism in
patients with CKD on
dialysis
Abaloparatide 2017 Synthetic Parathyroid hormone
receptor 1 (PTR-1) agonist
Osteoporosis
Semaglutide 2017 rDNA technology GLP-1 receptor agonist T2DM
Lutetium Lu 177
dotatate
2018 Synthetic Binds to somatostatin
receptors subtype-2
Gastroenteropancreatic
neuroendocrine tumors
Ivosidenib 2018 Synthetic Isocitrate
dehydrogenase-1 inhibitor
Relapsed or refractory
acute myeloid leukemia
cholangiocarcinoma
Bremelanotide 2019 Synthetic Melanocortin receptor
(MCR) agonist
Hypoactive sexual desire
disorder in
premenopausal women
Afamelanotide 2019 Synthetic Melanocortin-1 receptor
(MC1R) agonist
Patients with phototoxic
reactions (damage to
skin) from erythropoietic
protoporphyria
Gallium Dotatoc
Ga-68
2019 Synthetic
Binds to somatostatin
subtype 2 receptors
(SSTR2)
PET imaging of
neuroendocrine tumors
Gallium Ga-68
gozetotide
2020 Synthetic Binds to prostate-specific
membrane antigen
(PSMA)
PET imaging of PSMA
for prostate carcinoma
Copper Dotatate
Cu-64
2020 Synthetic Binds to somatostatin
receptors with the highest
affinity for subtype 2
receptors (SSTR2)
PET/CT imaging of
neuroendocrine tumors
Setmelanotide 2020 Synthetic Melanocortin receptor 4
agonist
Obesity
Vosoritide 2021 Synthetic Atrial natriuretic peptide
receptor 2 agonist
Growth in children with
achondroplasia
Pegcetacoplan 2021 mRNA display Complement protein
C3 inhibitor
Paroxysmal nocturnal
hemoglobinuria (PNH)
Melphalan
flufenamide
2021 Synthetic DNA cross-linking and
alkylation
Multiple myeloma
Lonapegsomatropin-
TCGD (Skytrofa)
2021 rDNA technology Release somatotropin,
growth hormone receptor
agonist
Short stature
(Continued)
336
Table 15.1 (Continued)
Peptide therapeutic
Approval
year
Method of
development
Target pharmacological
action Indication
Difelikefalin 2021 Synthetic Kappa-type opioid
receptor agonist
Pruritus associated with
CKD patients on dialysis
Odevixibat 2021 Synthetic Ileal sodium/bile acid
transporter (IBAT)
inhibitor
Pruritus associated with
progressive familial
intrahepatic cholestasis
(PFIC)
Dasiglucagon 2021 Synthetic Glucagon receptor agonist Hypoglycemia
Voclosporin 2021 Synthetic Calcineurin inhibitor Lupus nephritis
Lutetium (
177
Lu)
vipivotide tetraxetan
2022 Synthetic DNA denaturation and
apoptosis
Metastatic prostate
cancer
Tirzepatide 2022 Synthetic GIP/GLP-1 dual agonist T2DM
Table 15.2 Peptide-based drugs in clinical trials.
Therapeutic
peptide candidate Peptide nature Indication
Phase
of trial Trial number
Bovine lactoferin Lactoferin-derived peptides Infant lactose intolerance 1 NCT04738058
Dulaglutide Analogue of GLP-1
Cessation of smoking 2
NCT03204396
Efinopegdutide IgG4 conjugated peptide Fatty liver 2 NCT04944992
Ghrelin Side chain modified ghrelin Obesity 1 NCT02953587
Somapacitan Human growth hormone
analog
Children growth hormone
deficiency
3 NCT03811535
Thymalfasin Modified prothymosin Cancer of thymus gland 2 NCT0366764
Vosoritide CNP cyclic derivative Achondroplasia 2 NCT03989947
Angiotensin 1-7 Angiotensin synthetic
analogue
Treatment of hypertension 1 NCT02245230
Deslorelin Gonadotropin releasing
hormone agonist
Breast cancer 2 NCT00080756
Thyrotropin Recombinant thyrotropin Cancers of head and neck 3 NCT00415233
K27M Peptide vaccine Brain tumors 2 NCT02960230
Ivosidenib Inhibitor of IDH1 Acute myeloid leukemia,
solid tumors
1 NCT04176393
LSALT peptide Linear peptide COVID-19 2 NCT04402957
LY3437943 Analogue of proglucagon Obesity treatment 2 NCT0846778
IB1362 Synthetic peptide T2DM, obesity 2 NCT04440345
AZP-3601 Analog of parathyroid
hormone
Hyperthyroidism 1 NCT05239221
Metreleptin Leptin synthetic analogue Type 2 diabetes,
hyperlipidemia
2 NCT00085982
Avexitide GLP-1 antagonist Obesity 2 NCT02697253
337
Table 15.2 (Continued)
Therapeutic
peptide candidate Peptide nature Indication
Phase
of trial Trial number
Motixafortide Heterodetic cyclic peptide,
CXCR4 inhibitor
Multiple myeloma 1 NCT05293171
Trofinetide Synthetic analog and terminal
tripeptide of IGF1
Rett syndrome 3 NCT04279314
Cagrilintide Novel lipidated amylin analog T2DM 2 NCT04982575
Rusfertide Hepcidin mimetic Polycythemia vera 2 NCT04767802
AXT107 20-mer amino acid derived
from the sequence in type IV
collagen edema
Diabetic macular and
neovascular age-related
macular degeneration
2 NCT04279314
Zilucoplan Synthetic macrocyclic peptide
inhibitor
Amyotrophic lateral
sclerosis, myasthenia gravis
3 NCT04436497
Aviptadil Octacosapeptide vasoactive
intestinal peptide analog
COVID-19 3 NCT04843761
Zetomipzomib P1 keto-epoxide-containing
peptide
Polymyositis/
dermatomyositis, Lupus
nephritis, erythematosus
2 NCT04033926
Bulevirtide Lipopeptide Chronic hepatitis delta 3 NCT03852719
Glepaglutide Long-acting GLP2 analog Short bowel syndrome III
2018
3 NCT03690206
Setmelanotide Cyclic peptide analog of
pro-opiomelanocortin
Rare genetic disorders of
obesity
3 NCT03013543
Adegramotide Peptide vaccine Renal cell carcinoma,
urothelial carcinoma,
glioblastoma
3 NCT0331133
Mifamuritide Synthetic derivative of
muramyl dipeptide
Osteosarcoma 2 NCT01459484
Cu-64 TP3805 Activator of pituitary cyclic
adenylate
Bladder cancer 1 NCT03039413
Cyclization
C-terminal
modification
Insertion of non-
canonical amino acids
N-terminal
modification
Side chain
modification
Backbone
modification
O
O
OH
O
O
H
2
N
H
N
H
N
N
H
R
1
R
3
R
2
R
4
Figure 15.3 Peptide diversification strategies.
338
15.2.5.1 Chemical Synthesis of Peptides
Ever since the introduction of solid phase synthesis (SPSS) of peptides by Merrifield [6], the development
of peptides has become easier, more accessible, and efficient enough. SPSS is one of the major
methods for current day peptide synthesis in terms of methodology and synthetic materials
used. SPSS was the perfect alternative approach to the time-consuming and less convenient clas-
sical solution phase synthetic methods, which necessitated purification after each cycle of amino
acid coupling [88]. Precisely, in SPSS, the N-protected C-terminal amino acid is covalently
attached via the carboxylic group to an insoluble amino or hydroxyl to finally yield a C-terminal
amide peptide or C-terminal acid, respectively. Further, the peptide chain is elongated in the
C-terminus to the N-terminus strategy through a series of coupling and deprotection steps. The
α-amino groups are protected by either Boc (t-butyloxycarbonyl)/Fmoc (fluroenylmethyloxycar-
bonyl) groups to avoid side reactions with reagents used in the synthesis process (Figure 15.1).
The protecting groups and peptidyl resins are removed by employing strong anhydrous hydro-
gen fluoride or trifluromethanesulfonic acid in Boc-SPSS and trifluoracetic acid in Fmoc-SPSS,
respectively [89, 90]. Of note, the removal of Fmoc is achieved in milder conditions, thereby
making Fmoc-SPSS a method of choice for peptide synthesis [91]. The Boc-based SPSS employs
Merrifield resin for the synthesis of C-terminus acid peptides, whereas MBHA resin is used for
C-terminus amide peptides. On a similar note, Fmoc-based SPSS uses Pal resin, Rink resin, and
Sieber resin to synthesize C-terminus amide peptides. Trityl chloride resin, 2-chloro trityl chlo-
ride resin, HMPB resin, Wang resin, and Sasrin resin are widely used for the synthesis of
C-terminus acid peptides [88]. A wide range of functional resins have been developed by cou-
pling various linkers to resins and are being frequently used for the synthesis of longer peptides
and peptide cyclization [92].
The synthesis of long peptides by SPSS still remains challenging due to interchain aggregation
and formation of aspartimide segments specially in Fmoc-SPSS, which reduces the purity of crude
peptides. Several methods, like the application of microwaves, using low substitution resins, using
mixed solvents, and introducing pseudoproline into reaction media, have been undertaken to
reduce reaction time, to separate the peptide chain, and more importantly to avoid aggregation
during the synthesis phase [93–96]. The formation of aspartimide during Fmoc SPSS is negated by
using microwaves for reaction, using N-α-alkyl Asp-Gly dipeptide, or by addition of 1-hydroxy
benzotriazole (HOBt), Oxyma Pure to reaction medium [97–100].
Very long peptides (>50 amino acids) are difficult to synthesize via SPSS. However, several che-
moselective ligation techniques were conjugated with SPSS to facilitate the smooth synthesis of
long peptides. In the chemical ligation method, a C-terminus thiocarboxylic acid group is used for
coupling with N-terminal amine through a peptide bond analogous linker. Alternatively, an acti-
vated thioester group at the C-terminus of one peptide can act as a strong nucleophile to attack the
N-terminus amine of another peptide segment [101, 102]. Several other developed chemoselective
ligation techniques for the synthesis of peptides are briefly presented in Table 15.3.
Other techniques developed is the expressed protein ligation (EPL) [109] and sequential protein
ligation (SPL) [110]. Both methods are ideal for the synthesis of semisynthetic proteins. The semi-
synthetic proteins are synthesized chemoselectively ligating recombinant peptides and SPSS-
constructed peptides. Nonnatural amino acids can be incorporated into the peptide segments via
EPL and SPL. Currently, automated peptide synthesizers are used for lab scale synthesis of peptides.
CEM liberty PRIME and CSBio-II are automatic peptide synthesizers that utilize microwave or
infrared heat to sequentially ligate peptides [111]. Microwave and infrared heating have limited
application for large-scale peptide synthesis owing to risks of overheating and lack of larger
equipment [112].
Table 15.3 Chemical ligation techniques for peptide synthesis.
Ligation technique Linker functional group Methodology Reference
Thioester ligation Peptide segment 1-CO-S-peptide segment 2 Nucleophilic attack by thioacid sulfur of N-terminal peptide at alkyl
halide of C-terminal peptide
[103]
Oxime ligation Peptide segment 1-CH═NO-peptide segment 2
Condensation of aldehyde functional groups at the C-terminus of the
N-terminal peptide with aminooxy groups at the N-terminus of the
C-terminal peptide
[104]
Hydrazone ligation Peptide segment 1-CH═NNH-peptide
segment 2
Condensation of aldehyde functional groups at the C-terminus of the
N-terminal peptide with hydrazine groups at the N-terminus of the
C-terminal peptide
[105]
Thiazolidine/Oxazolidone
ligation
OH
X
R
O
O
Peptide 2
Peptide 1
N
X=S/O; R=H, CH
3
Formation of thiazolidine/oxazolidone capture device between
C-terminal peptide ester aldehyde and N-terminal thiol/hydroxyl
amine group
[106]
Native chemical ligation
Peptide 2
O
O
SH
Peptide 1
H
N
N
H
Ligation between thioester at the C-terminus of one peptide and
cysteine residue at the N-terminus of another peptide following
spontaneous rearrangement of thioester bond to amide bond
[107]
Thioacid capture ligation
SH
O
C
Peptide 2
Peptide 1 NH
Thioacid from C-terminal peptide capture by NPYS (5-nitropyridyl-2-
sulfenyl) activated cysteine thiol of N-terminal peptide leading to form
ligated peptide via acyl disulfide intermediate
[108]
340
15.2.5.2 Chemical Modification of Peptide and Peptidomimetics
Chemical diversification of peptides generally involves late-stage modifications and peptidomimetic
strategies. The modification of peptide structure is important for mimicking, stabilizing, or
constructing a superlative secondary structure to enhance their biological [113]. Prior to chemi-
cal modification, an alanine scan is carried out to determine key residues that impart biological
properties to lead peptide [114, 115]. Peptidomimetics structurally possess a pharmacophore
that mimic peptide structures and display pharmacological action. Peptidomimetics are instru-
mental in abrogating pharmacokinetic disadvantages of therapeutic peptides [7]. Based on
their structural features, the peptidomimetics have been divided into four groups [116]. Class A
comprises peptidomimetics that have minute modifications in their backbone or amino acid
sequences like voclosporin and trofinetide. Class B peptidomimetics have incorporated nonca-
nonical amino acids in their basic sequence [117]. The incorporation of unnatural amino acids
in peptides improves the inherent pharmacokinetic and pharmacodynamic properties.
Odevixibat (2021) and setmelanotide (2020) are exquisite examples of FDA-approved therapeu-
tic peptides having unnatural amino acids in their peptide sequence. Class C peptidomimetics
are modified peptides wherein the amide bonds are replaced by oxetane, aza, or triazole link-
ages. Saquinavir is a good example of backbone-modified peptide. Class D peptidomimetics are
small drug molecules that only mimic the pharmacological activity of the nascent peptide with-
out any structural resemblance or side-chain modifications, such as navitoclax and venetoclax
(BH3 mimetics).
15.2.5.3 Backbone Modification of Peptides
Backbone diversifications uplift the physicochemical properties of therapeutic peptides [118]. The
backbone modifications of the peptide could be removable so as to improve solubility by inserting
soluble polyarginine tags and facilitating synthesis or nonremovable where unnatural amino acids
are inserted in the nascent peptide for improving the pharmacology [119, 120].
The basic strategies for nonremovable modifications involve Cα-methylation, backbone cycliza-
tions, and Nα-methylations. The insertion of noncanonical amino acids in the peptide reduces
flexibility and thereby imparting tertiary structure to the modified peptide [121–123].
Replacing an α-amino acid with a side chain bearing amino acid on β3 carbon prolongs half-lives
of peptides [124, 125]. Selepressin has a prolonged plasma half-life developed by the backbone
modification of vasopressin [126]. Backbone modification of cyclic peptides by N-methylations
has improved their membrane permeability and oral bioavailability [127].
15.2.5.4 Side-Chain Modification of Peptides
By replacing the canonical amino acids from the parent peptides with their respective analogs,
side-chain modifications can be achieved. Such side-chain modifications make the peptide target
specific with improved binding affinity [128]. Β-phenylalanine, homoarginine, and benzyloxyty-
rosine are some analogs of natural amino acids also available commercially and have been success-
fully used for side-chain modifications [129, 130]. Liraglutide and semaglutide are the GLP-1
agonists with side-chain modifications [131].
15.2.5.5 Peptide Cyclization
In the roadway of uplifting the biophysical characteristics of the peptides as well as broadening
their applicability as biocatalysts and therapeutics, cyclization is an escalating field of research.
Cyclization enhances biological activity, target binding specificity, cell permeability, and meta-
bolic stability of therapeutic peptides [132]. The peptides can be cyclized in four different
341
orientations: side chain-to-side chain, head-to-tail, head-to-side chain, and tail-to-side chain
(Figure 15.4). Peptide cyclization can be achieved by chemical, enzymatic, and protein tagging
techniques [133].
The chemical methods encompass direct amide bond formations, native chemical ligations,
C-terminal aldehyde ligations, disulfide bond formations, and biorthogonal reactions. Direct
amide bond formation is achieved by converting the C-terminal –OH into a better-leaving group
using a single or combination of coupling agents along with tertiary amine base additive like
DIEA [134]. Backbone peptide cyclization of peptides can be achieved by intramolecular native
chemical ligations even at millimolar concentrations [135]. Several cyclic peptides like dapto-
mycin [136], cyclomontanin B [137], and many more are developed from chemical ligations
where a C-terminal glycolaldehyde reacts with N-terminal serine or threonine residue to form
a benzylidene acetal amide intermediate that rearranges to form peptide bond [138]. More
recently, the CyClick method has been applied for the synthesis of thermodynamically stable
bicyclic peptides [139]. Biorthogonal reactions are also extensively used for the synthesis of
cyclic peptides. The commonly used biorthogonal reactions are Staudinger ligations [140],
KAHA ligations [141], TAMM ligations [142], CuAAC cycloadditions, and RuAAC cycloaddi-
tions [143]. Cyclization through disulfide bond formation can be achieved by the insertion of
orthogonal cysteine residues in peptide chains [144]. Using disulfide stapling agents, strong
thioether linkages are established between the cysteine residues which make the cyclic peptide
more stable biophysically [145].
Cyclic peptides are also synthesized by employing enzymes. Subglitases [146], sortases [147],
and asparaginyl transpeptidases are used for the backbone cyclization of many peptides. Amino
acid side chains can be ligated using transglutaminases as well [148]. Noncatalytic protein domains
also called as tags are conjugated to peptide of interest for initiating cyclization. Inteins [149], Spy
tag/Spy catcher [150], and Snoop tag/Snoop catcher [151] exclusively used tags for the synthesis of
cyclic peptides.
NH
2
NH
2
NH
2
C
C
O
O
COOH
COOH
NH
COOH
R
2
R
2
R
2
Tail to side chain
Side chain-side chain
Peptide chain
HN
Head to tail
Head to side chain
R
1
R
1
R
1
R
1
R
2
R
1
R
2
Figure 15.4 Strategies for peptide cyclization.
342
15.2.5.6 Peptide Mimicking of α-Helices and Stabilization
Hydrogen bond surrogates or stabilized α-helices are produced by replacing hydrogen bonds
with covalent bonds in the parent peptide chain [152]. The α-helices can also be stabilized by
inserting cross-links in the amino acid side chains. Building crosslinks at i and i + 4 as well as i
and i + 7 positions in the α-helix side chains is very effective in producing stable peptide struc-
tures [153]. Stable α-helices are also produced by inserting lactam-based cross-links, disulfide
bonds, and biselctrophillic linkers [154–156]. Stapling of peptides is currently used in innova-
tive cross-linking approaches for stabilizing α-helices. The technique forms nucleophilic cross-
links via insertion of electrophilic unnatural amino acid residues at i and i + 4 as well as i and
i + 7 positions [157].
15.2.5.7 Peptide Mimicking of β-Strands and β-Sheets
The design of peptidomimetics and peptides for targeting secondary structures in various PPIs is a
burgeoning research area. β-Strands and sheets are secondary structures of proteins. -proline and
-proline templates are being majorly used for stabilizing β-hairpins in PPI inhibitors [158]. Some
notable peptide mimetic strategies employed for targeting PPIs involving destabilized β-strands
and β-sheets are showcased in Table 15.4.
15.2.5.8 Peptide Production by Recombinant Technology
Cheaper, sustainable, and scalable bioactive peptide production is enabled by recombinant DNA
technology. The expression systems used are bacteria, yeast, mammalian cells, insect cell cultures,
and plants [166]. The basic strategy encompasses genome modification of the host/expression sys-
tem by inserting gene encoding peptide or protein of interest followed by its expression in the host.
Later, the recombinant peptide/protein of interest is isolated and purified [167]. The first human
peptide to be produced recombinantly was somatostatin followed by insulin in 1982 [168, 169].
Table 15.5 displays various recombinant therapeutic peptides.
Table 15.4 Peptidomimetics for stabilization of β-sheet/β strands in PPIs.
Peptidomimetic strategy PPI aggregations Target disorder Reference
Modified β6 and β7 strands of
SOD1 (β-strand mimics)
SOD1 (superoxide
dismutase-1)
ALS (amyotrophic lateral
sclerosis)
[159]
Isolated sequence recognition
elements (β-strand mimics)
Amyloid β-peptide (segments
1–42)
Alzheimer’s disease [160]
Linear peptide with β-sheet
breakers
Insulin aggregation Impaired insulin absorption [161]
Cyclic β-hairpins Dimerization of epithelial
growth factor receptor
Carcinomas [162]
Acyclic β-hairpins Transthyretin aggregation Familial amyloid
polyneuropathy
[163]
Tweezer molecules Dimerization of HIV-1
protease
AIDS [164]
Peptide antibodies Human α-synuclein
aggregation
Parkinson’s disease [165]