Structural and charge requirements for antimicrobial and hemolytic activity in the peptide PKLLETFLSKWIG, corresponding to the hydrophobic region of the antimicrobial protein bovine seminalplasmin

Abstract

Several analogs of the 13-residue antimicrobial and hemolytic peptide PKLLETFLSKWIG (SPF), which is the most hydrophobic region of the 47-residue antimicrobial protein seminalplasmin [ Sitaram, N. & Nagaraj, R. (1990) J. Biol. Chem. 265, 10438-104423 have been synthesized. The antimicrobial and hemolytic properties of the peptides were investigated with a view to gain an insight into the structural and charge requirements for these activities of SPF. Peptides in which E was replaced by K exhibited considerably improved antimicrobial activity with no concomitant increase in hemolytic activity. A peptide in which the aromatic amino acids were replaced by leucine exhibited antimicrobial activity like those of the peptides which had aromatic amino acids. Interchange in the positions of E and K and total replacement of K by E resulted in complete loss of activity. The peptides having antimicrobial activities showed appreciable helical content in a hydrophobic environment, whereas inactive peptides did not. Thus, by suitable 'engineering' the biological activity of a short 13-residue peptide can be altered to yield peptides specifically having only antimicrobial activity with increased potency. 0 Munksgaard 1995.

Membrane disruptive antimicrobial activities of human β-defensin-3 analogs

“…The primary objective of this study is to understand the mechanism of interaction between HβD-3 and the model lipid membranes, in order to explain its biological activities against bacteria and blood cells. Therefore, it is mandatory to work on the native sequence to narrow down the minimal required sequence for the antimicrobial activity to subsequently synthesize the active analogues [23, 24]. …”

iAMAP-SCM: A Novel Computational Tool for Large-Scale Identification of Antimalarial Peptides Using Estimated Propensity Scores of Dipeptides

“…The amphiphilic property enhances cellular membrane permeability through ion channel formation and thus disrupts the lipid bilayer. , In general, peptides acting on membranes exhibit their amphipathic activity in secondary structure form once they are in a membrane environment . Owing to the potent clinical relevance of membrane active peptides, the correlation of AMP structure–function relationship has been extensively investigated. − The formation of amphipathic conformations can be observed when the cationic amphipathic peptides are located in membrane environments. − Notably, other conformations can also result in an amphipathic separation of hydrophobic and polar residues, efficient membrane interactions, and antimicrobial activities. , The amphipathic separation of hydrophobic and polar residues illustrates the specific interactions of AMPs with the phospholipid membrane interfaces …”

“… 85 Owing to the potent clinical relevance of membrane active peptides, the correlation of AMP structure–function relationship has been extensively investigated. 85 − 88 The formation of amphipathic conformations can be observed when the cationic amphipathic peptides are located in membrane environments. 89 − 91 Notably, other conformations can also result in an amphipathic separation of hydrophobic and polar residues, efficient membrane interactions, and antimicrobial activities.…”

Characterization and Antimicrobial Activity of Amphiphilic Peptide AP3 and Derivative Sequences

“…However, the high concentrations required for antibacterial activity indicate there may be limited selectivity in these peptides. Many studies linked the cytotoxic effects of AMPs and AMP mimetics to hydrophobic interactions, in which increased hydrophobic content is proportional to increased cytotoxicity [16,17,18,66,67]. Notably, the peptides with the best antimicrobial activity, AP3 and AP3K, were also the most cytotoxic.…”