Peptidology: short amino acid modules in cell biology and immunology

Abstract

Short amino acid motifs, either linear sequences or discontinuous amino acid groupings, can interact with specific protein domains, so exerting a central role in cell adhesion, signal transduction, hormone activity, regulation of transcript expression, enzyme activity, and antigen-antibody interaction. Here, we analyze the literature for such critical short amino acid motifs to determine the minimal peptide length involved in biologically important interactions. We report the pentapeptide unit as a common minimal amino acid sequence critically involved in peptide-protein interaction and immune recognition. The present survey may have implications in defining the dimensional module for peptide-based therapeutical approaches such as the development of novel antibiotics, enzyme inhibitors/activators, mimetic agonists/antagonists of neuropeptides, thrombolitic agents, specific anti-viral agents, etc. In such a therapeutical context, it is of considerable interest that low molecular weight peptides can easily cross biological barriers, are less susceptible to protease attacks, and can be administered at high concentrations. In addition, small peptides are a rational target for strategies aimed at antigen-specific immunotherapeutical intervention. As an example, specific short peptide fragments might be used to elicit antibodies capable of reacting with the full-length proteins containing the peptide fragment's amino acid sequence, so abolishing the risk of cross-reactivity.

The self/nonself issue: A confrontation between proteomes

“…15,16 Generally, the lack of success in B-cell epitope definition is due, mainly, to the difficulties associated with the task. The optimal amino acid (aa) length of a B-cell epitope is five aa, 17 but longer epitopes have been described. In general, linear B-cell epitopes have been described as varying in length, with up to 16 residues reported.…”

“…a Low similarity 5-mer given in capital letters. Based on the minimum length of an immune unit of 5-6 amino acids, 17 each epitope has been dissected into pentapeptide sequences. The pentapeptides overlapped by four residues, i.e., were shifted by one amino acid.…”

1-Methoxycarbonyl-2-(4-nitrophenyl)ethanaminium nitrate

“…For details of -amino acid derivatives, see: Lucchese et al (2007); Arki et al (2004); Hauck et al (2006); Dai & Fu (2008); Wen (2008); Azim et al (2006).…”

“…Amino acid derivatives are important compounds due to their biological activities, and there has been an increased interest in the enantiomeric preparation of α-amino acid derivatives as precursors for the synthesis of novel biologically active molecules (Lucchese et al, 2007;Arki et al, 2004;Hauck et al, 2006;Azim et al, 2006;Dai et al, 2008;Wen, 2008). Here we report the crystal structure of the title compound.…”

Nullomer derived anticancer peptides (NulloPs): Differential lethal effects on normal and cancer cells in vitro

“…While combinatorial and phage display libraries have been used to generate peptide drugs that were not derived from nature, we have taken a completely new approach to look for effective cancer drugs; we look specifically for what does not exist [21] in nature. Acquisti et al have dismissed this approach [1], claiming that absent sequences are actually a consequence of mutation and will not be useful for medical or labeling purposes; but others have explored the distribution of absent sequences suggesting possible applications [7,31,42]. We have used a new algorithm for this negative in-silico selection that enables us to identify small epitopes with possible lethal effects [21].…”