143192-31-8Relevant articles and documents
Peptide/peptoid hybrid oligomers: The influence of hydrophobicity and relative side-chain length on antibacterial activity and cell selectivity
Frederiksen, Nicki,Hansen, Paul R.,Bj?rkling, Fredrik,Franzyk, Henrik
, (2019/12/26)
Previous optimisation studies of peptide/peptoid hybrids typically comprise comparison of structurally related analogues displaying different oligomer length and diverse side chains. The present work concerns a systematically constructed series of 16 closely related 12-mer oligomers with an alternating cationic/hydrophobic design, representing a wide range of hydrophobicity and differences in relative side-chain lengths. The aim was to explore and rationalise the structure-activity relationships within a subclass of oligomers displaying variation of three structural features: (i) cationic side-chain length, (ii) hydrophobic side-chain length, and (iii) type of residue that is of a flexible peptoid nature. Increased side-chain length of cationic residues led to reduced hydrophobicity till the side chains became more extended than the aromatic/hydrophobic side chains, at which point hydrophobicity increased slightly. Evaluation of antibacterial activity revealed that analogues with lowest hydrophobicity exhibited reduced activity against E. coli, while oligomers with the shortest cationic side chains were most potent against P. aeruginosa. Thus, membrane-disruptive interaction with P. aeruginosa appears to be promoted by a hydrophobic surface of the oligomers (comprised of the aromatic groups shielding the cationic side chains). Peptidomimetics with short cationic side chains exhibit increased hemolytic properties as well as give rise to decreased HepG2 (hepatoblastoma G2 cell line) cell viability. An optimal hydrophobicity window could be defined by a threshold of minimal hydrophobicity conferring activity toward E. coli and a threshold for maximal hydrophobicity, beyond which cell selectivity was lost.
Building Units for N-Backbone Cyclic Peptides. 1. Synthesis of Protected N-(ω-Aminoalkylene)amino Acids and Their Incorporation into Dipeptide Units
Byk, Gerardo,Gilon, Chaim
, p. 5687 - 5692 (2007/10/02)
A variety of new amino acids which contain an ω-aminoalkylene group on the Nα-amino nitrogen were synthesized by alkylation of alkylenediamines with α-halogeno acids.The reaction proceeds with inversion of configuration; thus, optically pure products were obtained when optically active α-halogeno acids were used.The N-(ω-aminoalkylene)amino acids were protected by orthogonal protecting groups to allow their incorporation into dipeptides by the "solution" techniques and into peptides by the solid-phase peptide synthesis (SPPS) methodology.A series of dipeptide analogs of Phe-Gly, Leu-Gly, Trp-Gly, Phe-Leu, and Phe-Ala in which the nitrogen of the peptide bond is alkylated by ω-aminoalkylene chains with various lengths were prepared.These new protected N-(ω-aminoalkylene)amino acids and their derived dipeptide units may be used as building blocks for conformationally constrained N-backbone cyclic peptides.
