Design, synthesis, conformational and membrane ion transport studies of proline‐adamantane hybrid cyclic depsipeptides

Abstract

The design, synthesis, conformational, crystallographic, and ion transport studies of 30‐membered, proline containing depsipeptides that incorporate the rigid low molecular weight lipophilic adamantane (Adm) building blocks are reported. The adamantyl groups provide the desired membrane permeability and conformational constraint for efficient transport in lipid membranes. The novel cyclic depsipeptides are: c[AdmC(O)Pro OCH2 CHRNHC(O)ProC(O) AdmC(O)ProC(O)NHCHRCH2 OProC(O)] where RH for A and RCONHAdm for B. Crystal structure analysis of A established that the two peptide segments are identical in formula and in conformation and that the peptides are bonded to the interleaving Adm at the 1 and 3 positions. However, the complete ring is highly asymmetric in shape since bonds for both Peptide‐Adm‐Peptide segments have the syn‐anti motif. Torsional angles for the connecting bonds to Adm are −162°, +71° and −169°, −48°. The irregular clamshell shape of the molecule has three internal CO moieties directed in a manner that could provide three Na+O ligands. While A exhibited negligible transport of Na+ ions across membranes, peptide B endowed with two additional adamantanes in the periphery did transport Na+ ions from outside to inside. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 471–478, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

Synthesis,68Ga-Radiolabeling, and PreliminaryIn VivoAssessment of a Depsipeptide-Derived Compound as a Potential PET/CT Infection Imaging Agent

“…Alanine has a higher α -helical-forming tendency than glycine. The major conformational feature is β -turn, involving glycine and proline [ 16 ].…”

Co-assembled Coiled-Coil Peptide Nanotubes with Enhanced Stability and Metal-Dependent Cargo Loading

“…While less common than simpler nanofibrils, these three-dimensional materials contain an inner cavity and outer shell to allow for multifunctionality. Peptide-based nanotubes specifically are an attractive choice owing to their tunability and biocompatibility. − As such, peptide nanotubes have been derived from a diverse collection of structures including dipeptides, − cyclic peptides, − peptoids, − triple helices, , β-sheets, − and coiled-coils. − …”

“…The assembly and morphology of peptide nanotubes provide the opportunity for a range of interesting biological applications. For example, early studies with cyclic peptide nanotubes focused on interactions with the cell membrane to mimic membrane-bound proteins and form ion channels. ,,− , Since then, nanotubes have been developed with antibacterial properties, including dipeptide nanotubes clearing biofilms and cyclic peptide nanotubes lysing bacterial membranes. , β-sheet nanotubes have been used for directed delivery of an anticancer agent to metastatic melanoma, whereas coiled-coil nanotubes, composed of the peptide TriNL (Figure A), for instance, have been loaded with a biopolymer cargo …”