Use of Parallel Synthesis To Probe Structure−Activity Relationships among 12-Helical β-Peptides:  Evidence of a Limit on Antimicrobial Activity

• Published in: Journal of the American Chemical Society Vol. 127; no. 32; pp. 11516 - 11529
• Main Authors: Porter, Emilie A, Weisblum, Bernard, Gellman, Samuel H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.08.2005; Amer Chemical Soc
• Subjects: Amino Acid Sequence; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Biological and medical sciences; Chemistry; Chemistry, Multidisciplinary; Escherichia coli - drug effects; Exact sciences and technology; General pharmacology; Gram-Positive Bacteria - drug effects; Medical sciences; Molecular Sequence Data; Organic chemistry; Peptide Library; Peptides; Pharmacology. Drug treatments; Physical Sciences; Physicochemical properties. Structure-activity relationships; Preparations and properties; Protein Structure, Secondary; Science & Technology; Structure-Activity Relationship; HELICAL SECONDARY STRUCTURE; DE-NOVO DESIGN; MAGAININ; ANALOGS; STABILITY; EFFICIENT ROUTE; RESISTANCE; DIASTEREOMERS; 2-AMINOCYCLOPENTANECARBOXYLIC ACID-DERIVATIVES; AQUEOUS-SOLUTION; Oligomerization; Structure activity relation; Chemical compound library; Helical structure; Peptide synthesis; Secondary structure; Structure function relationship; Circular dichroism

We report structure−activity trends among helix-forming β-amino acid oligomers that are intended to mimic α-helical host-defense peptides. Parallel synthesis of two small, focused β-peptide libraries allowed us to identify relatively short (11-residue) β-peptides that display antimicrobial activity....