Exploring the Antibacterial and Hemolytic Activity of Shorter‐ and Longer‐Chain β‐, α,β‐, and γ‐Peptides, and of β‐Peptides from β²‐3‐Aza‐ and β³‐2‐Methylidene‐amino Acids Bearing Proteinogenic Side Chains – A Survey

Abstract

The antibacterial activities of 31 different beta-, mixed alpha/beta-, and gamma-peptides, as well as of beta-peptides derived from beta2-3-aza- and beta3-2-methylidene-amino acids were assayed against six pathogens (Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), and the results were compared with literature data. The interaction of these peptides with mammalian cells, as modeled by measuring the hemolysis of human erythrocytes, was also investigated. In addition to those peptides designed to fold into amphiphilic helical conformations with positive charges on one face of the helix, one new peptide with hemolytic activity was detected within the sample set. Moreover, it was demonstrated that neither cationic peptides used for membrane translocation (beta3-oligoarginines), nor mixed alpha/beta- or gamma-peptides with somatostatin-mimicking activities display unwanted hemolytic activity.

Genetic Variation in Spatio-Temporal Confined USA300 Community-Associated MRSA Isolates: A Shift from Clonal Dispersion to Genetic Evolution?

“…The genes are most similar to a V8 protease, which can cleave the heavy chain of human immunoglobulin classes in vitro. In 64% of the isolates the s pl operon was present and no obvious role in virulence was demonstrated in intraperitoneally injected rats [22], [29].…”

De Novo Design of Antimicrobial Polymers, Foldamers, and Small Molecules: From Discovery to Practical Applications

“…Our group47,48 as well as those of Gellman49 and Seebach50 independently showed that β-peptides capable of forming amphiphilic 14- or 12-helices had potent antimicrobial activity. Oligomers with lengths of 10-15 residues that achieved an appropriate hydrophilic/lipophilic balance were selective for killing bacteria vs. mammalian cells.…”

A Novel β-Peptidyl Aminopeptidase (BapA) from Strain 3-2W4 Cleaves Peptide Bonds of Synthetic β-Tri- and β-Dipeptides

“…Furthermore, first studies on the stability of ␤-peptides in vivo have shown that virtually no degradation was observed when such peptides were administered to rats (42,43). Some ␤-peptides possess antimicrobial activities (4,5,25,38), bind to the human somatostatin receptor (12,21), function as inhibitors of human immunodeficiency virus type 1 replication (39), and inhibit p53-hDM2 interaction (18). Cationic ␤-peptides cross bacterial and mammalian cell membranes and can be considered a new group of cell-penetrating peptides (13,26,31).…”