Design of Peptides for Membrane Insertion: The Critical Role of Charge Separation.

ABSTRACT: A physical understanding of membrane permeation and translocation by small, positively charged molecules can illuminate cell penetrating peptide mechanisms of entry and inform drug design. We have previously investigated the permeation of the doubly charged peptide WKW and proposed a defect-assisted permeation mechanism where a small molecule with +2 charge can achieve a metastable state spanning the bilayer by forming a membrane defect with charges stabilized by phospholipid phosphate groups. Here, we investigate the membrane permeation of two doubly charged peptides, WWK and WWWK, with charges separated by different lengths. Through complementary experiments and molecular dynamics simulations, we show that membrane permeation was an order of magnitude more favorable when charges were sep

SUBMITTER: Povilaitis SC 

PROVIDER: S-EPMC9541189 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature