Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F20%3A00114328" target="_blank" >RIV/00216224:14740/20:00114328 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1021/acs.jpcb.0c03291" target="_blank" >https://doi.org/10.1021/acs.jpcb.0c03291</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.0c03291" target="_blank" >10.1021/acs.jpcb.0c03291</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes

Popis výsledku v původním jazyce

Biological membranes present a major obstacle for the delivery of therapeutic agents into cells. Some peptides have been shown to translocate across the membrane spontaneously, and they could be thus used as drug-carriers. However, the advantageous peptide properties for the translocation remain unclear. Of particular interest is the effect of a proline-induced kink in alpha-helical peptides, because the kink was previously reported to both increase and decrease the antimicrobial activity. The antimicrobial activity of peptides could be related to their translocation across the membrane as is the case of the buforin 2 peptide investigated here. Using computer simulations with two independent models, we consistently showed that the presence of the kink has (1) no effect on the translocation barrier, (2) reduces the peptide affinity to the membrane, and (3) disfavors the transmembrane state. Moreover, we were able to determine that these effects are mainly caused by the peptide increased polarity, not the increased flexibility of the kink. The provided molecular understanding can be utilized for the design of cell-penetrating and drug-carrying peptides.

Název v anglickém jazyce

Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes

Popis výsledku anglicky

Biological membranes present a major obstacle for the delivery of therapeutic agents into cells. Some peptides have been shown to translocate across the membrane spontaneously, and they could be thus used as drug-carriers. However, the advantageous peptide properties for the translocation remain unclear. Of particular interest is the effect of a proline-induced kink in alpha-helical peptides, because the kink was previously reported to both increase and decrease the antimicrobial activity. The antimicrobial activity of peptides could be related to their translocation across the membrane as is the case of the buforin 2 peptide investigated here. Using computer simulations with two independent models, we consistently showed that the presence of the kink has (1) no effect on the translocation barrier, (2) reduces the peptide affinity to the membrane, and (3) disfavors the transmembrane state. Moreover, we were able to determine that these effects are mainly caused by the peptide increased polarity, not the increased flexibility of the kink. The provided molecular understanding can be utilized for the design of cell-penetrating and drug-carrying peptides.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

The Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

1520-5207

Svazek periodika

124

Číslo periodika v rámci svazku

28

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

5940-5947

Kód UT WoS článku

000551541600017

EID výsledku v databázi Scopus

2-s2.0-85087670337