TY - JOUR

T1 - Self-assembly to function

T2 - design, synthesis, and broad spectrum antimicrobial properties of short hybrid E-vinylogous lipopeptides

AU - Shankar, S Shiva

AU - Benke, Sushil N

AU - Nagendra, Narem

AU - Srivastava, Prabhakar Lal

AU - Thulasiram, Hirekodathakallu V

AU - Gopi, Hosahudya N

PY - 2013/11/14

Y1 - 2013/11/14

N2 - Nonribosomal E-vinylogous γ-amino acids are widely present in many peptide natural products and have been exploited as inhibitors for serine and cysteine proteases. Here, we are reporting the broad spectrum antimicrobial properties and self-assembled nanostructures of various hybrid lipopeptides composed of 1:1 alternating α- and E-vinylogous residues. Analysis of the results revealed that self-assembled nanostructures also play a significant role in the antimicrobial and hemolytic activities. In contrast to the α-peptide counterparts, vinylogous hybrid peptides displayed excellent antimicrobial properties against various bacterial and fungal strains. Peptides that adopted nanofiber structures displayed less hemolytic activity, while peptides that adopted nanoneedle structures displayed the highest hemolytic activity.

AB - Nonribosomal E-vinylogous γ-amino acids are widely present in many peptide natural products and have been exploited as inhibitors for serine and cysteine proteases. Here, we are reporting the broad spectrum antimicrobial properties and self-assembled nanostructures of various hybrid lipopeptides composed of 1:1 alternating α- and E-vinylogous residues. Analysis of the results revealed that self-assembled nanostructures also play a significant role in the antimicrobial and hemolytic activities. In contrast to the α-peptide counterparts, vinylogous hybrid peptides displayed excellent antimicrobial properties against various bacterial and fungal strains. Peptides that adopted nanofiber structures displayed less hemolytic activity, while peptides that adopted nanoneedle structures displayed the highest hemolytic activity.

KW - Anti-Bacterial Agents/chemical synthesis

KW - Antifungal Agents/chemical synthesis

KW - Candida albicans/drug effects

KW - Dose-Response Relationship, Drug

KW - Drug Design

KW - Escherichia coli/cytology

KW - Hemolysis

KW - Lipopeptides/chemical synthesis

KW - Microbial Sensitivity Tests

KW - Microscopy, Atomic Force

KW - Molecular Structure

KW - Particle Size

KW - Structure-Activity Relationship

KW - Surface Properties

U2 - 10.1021/jm400884w

DO - 10.1021/jm400884w

M3 - Article

C2 - 24117107

VL - 56

SP - 8468

EP - 8474

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 21

ER -