A Global Review on Short Peptides: Frontiers and Perspectives

Abstract

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

Keywords: SARS-COV-2; altered peptide ligands; ant/super/agonists; aptamers; bilayer interactions; cancer; cell-penetrating peptides; constrained amino acids and peptide (bio)mimetics; cosmeceuticals; diketopiperazine; drug design and drug/gene delivery; short peptides; synthesis; vaccines.

Figure 1

Schematic representation of some symmetrical C^α,α-dialkylated glycine and chiral α-methylated residues.

Figure 2

Angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe), Losartan, V8 Losartan analogues (R = CH₂OH, COOH). The angiotensin II scheme depicts the pharmacophoric groups of the eight amino acids of angiotensin II.

Figure 3

Bio-complex containg 2,5-DKP moiety [1O6I.pdb].

Figure 4

Bio-complex showing the C-H⋯π Fmoc interaction (PDB code 3gs4) [131].

Figure 5

(A) Structures of Fmoc-protected ΨPro dipeptide units for Fmoc solid-phase synthesis (SPPS), (B) general scheme of ΨPro-aided SPPS.

Figure 6

(A) Structure of the O-acyl isodipeptide units for Fmoc SPPS, (B) general scheme of the O-acyl isopeptide method.

Figure 7

Representative snapshot of cationic peptides (red) adsorved into POPG (green)/POPE (blue) surfaces. Simulations were carried out using: (A) All atom model of Lipid bilayers and (B) Coarse grain model of vesicles. Water and ion sites were removed for visualization purposes.

Figure 8

Monocyclic, bicyclilc, and tricyclic cell-penetrating peptides containing arginine and tryptophan residues as molecular transporters.

Figure 9

Presentation systems in peptide aptamer development.

Figure 10

Major histocompatibility complex (MHC)-peptide-T cell receptor (TCR) trimolecular complex denotes amino acids from peptide TCR contact sites, where mutations result in APLs.

Figure 11

Selected peptide-based anti-viral agents against SARS-CoV-2.

Figure 12

Anti-inflammatory (DEQHLETELHTHLTSVLTANGFQ) and cytotoxic (KENPVLSLVNGMF, AGAPGG, AERQ, and RDTQ) peptides derived from non-edible marine organisms.