Effect of Helical Kink on Peptide Translocation across
Phospholipid Membranes

J 2020

Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes

BROŽEK, Radim, Ivo KABELKA and Robert VÁCHA

Basic information

Original name

Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes

Authors

BROŽEK, Radim (203 Czech Republic, belonging to the institution), Ivo KABELKA (203 Czech Republic, belonging to the institution) and Robert VÁCHA (203 Czech Republic, guarantor, belonging to the institution)

Edition

The Journal of Physical Chemistry B, Washington, D.C. American Chemical Society, 2020, 1520-6106

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10403 Physical chemistry

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.991

RIV identification code

RIV/00216224:14740/20:00114328

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1021/acs.jpcb.0c03291

UT WoS

000551541600017

Keywords in English

Free energy; Lipids; Peptides and proteins; Membranes; Conformation

Abstract

V originále

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.

Links

GA17-11571S, research and development project

Name: Amfifilní peptidy na fosfolipidových membránách

Investor: Czech Science Foundation

GA20-20152S, research and development project

Name: Proteinová přitažlivost a selektivita pro buněčné membrány

Investor: Czech Science Foundation

LM2015085, research and development project

Name: CERIT Scientific Cloud (Acronym: CERIT-SC)

Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

BROŽEK, Radim, Ivo KABELKA and Robert VÁCHA. Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes. The Journal of Physical Chemistry B. Washington, D.C.: American Chemical Society, 2020, vol. 124, No 28, p. 5940-5947. ISSN 1520-6106. Available from: https://dx.doi.org/10.1021/acs.jpcb.0c03291.

@article{1680660,
   author = {Brožek, Radim and Kabelka, Ivo and Vácha, Robert},
   article_location = {Washington, D.C.},
   article_number = {28},
   doi = {http://dx.doi.org/10.1021/acs.jpcb.0c03291},
   keywords = {Free energy; Lipids; Peptides and proteins; Membranes; Conformation},
   language = {eng},
   issn = {1520-6106},
   journal = {The Journal of Physical Chemistry B},
   title = {Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes},
   url = {https://doi.org/10.1021/acs.jpcb.0c03291},
   volume = {124},
   year = {2020}
}

TY  - JOUR
ID  - 1680660
AU  - Brožek, Radim - Kabelka, Ivo - Vácha, Robert
PY  - 2020
TI  - Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes
JF  - The Journal of Physical Chemistry B
VL  - 124
IS  - 28
SP  - 5940-5947
EP  - 5940-5947
PB  - American Chemical Society
SN  - 15206106
KW  - Free energy
KW  - Lipids
KW  - Peptides and proteins
KW  - Membranes
KW  - Conformation
UR  - https://doi.org/10.1021/acs.jpcb.0c03291
L2  - https://doi.org/10.1021/acs.jpcb.0c03291
N2  - 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.
ER  -

BROŽEK, Radim, Ivo KABELKA and Robert VÁCHA. Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes. \textit{The Journal of Physical Chemistry B}. Washington, D.C.: American Chemical Society, 2020, vol.~124, No~28, p.~5940-5947. ISSN~1520-6106. Available from: https://dx.doi.org/10.1021/acs.jpcb.0c03291.

Detailed Information on Publication Record