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 a Robert VÁCHA

Základní údaje

Originální název

Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes

Autoři

BROŽEK, Radim (203 Česká republika, domácí), Ivo KABELKA (203 Česká republika, domácí) a Robert VÁCHA (203 Česká republika, garant, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10403 Physical chemistry

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.991

Kód RIV

RIV/00216224:14740/20:00114328

Organizační jednotka

Středoevropský technologický institut

DOI

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

UT WoS

000551541600017

Klíčová slova anglicky

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

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 11. 2020 14:07, Mgr. Marie Šípková, DiS.

Anotace

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.

Návaznosti

GA17-11571S, projekt VaV

Název: Amfifilní peptidy na fosfolipidových membránách

Investor: Grantová agentura ČR, Amphiphilic Peptides at Phospholipid Membranes

GA20-20152S, projekt VaV

Název: Proteinová přitažlivost a selektivita pro buněčné membrány

Investor: Grantová agentura ČR, Protein Affinity and Selectivity to Cellular Membranes

LM2015085, projekt VaV

Název: CERIT Scientific Cloud (Akronym: CERIT-SC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CERIT Scientific Cloud

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

BROŽEK, Radim, Ivo KABELKA a 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, roč. 124, č. 28, s. 5940-5947. ISSN 1520-6106. Dostupné z: 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 a 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, roč.~124, č.~28, s.~5940-5947. ISSN~1520-6106. Dostupné z: https://dx.doi.org/10.1021/acs.jpcb.0c03291.

Podrobný výpis o publikaci