TY - JOUR

T1 - Why the Orientational Mobility in Arginine and Lysine Spacers of Peptide Dendrimers Designed for Gene Delivery Is Different?

AU - Безродный, Валерий Валерьевич

AU - Шавыкин, Олег Валерьевич

AU - Mikhtaniuk, Sofia E.

AU - Неелов, Игорь Михайлович

AU - Маркелов, Денис Анатольевич

AU - Шевелева, Надежда Николаевна

N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2020/12/2

Y1 - 2020/12/2

N2 - New peptide dendrimer with Lys-2Arg repeating units was recently studied experimentally by NMR (RSC Advances, 2019, 9, 18018) and tested as gene carrier successfully (Int. J. Mol. Sci., 2020, 21, 3138). The unusual slowing down of the orientational mobility of 2Arg spacers in this dendrimer was revealed. It has been suggested that this unexpected behavior is caused by the Arg-Arg pairing effect in water, which leads to entanglements between dendrimer branches. In this paper, we determine the reason for this slowing down using atomistic molecular dynamics simulation of this dendrimer. We present that the structural properties of Lys-2Arg dendrimer are close to those of the Lys-2Lys dendrimer at all temperatures (Polymers, 2020, 12, 1657). However, the orientational mobility of the H-H vector in CH 2-N groups of 2Arg spacers in Lys-2Arg dendrimer is significantly slower than the mobility of the same vector in the Lys-2Lys dendrimer. This result is in agreement with the recent NMR experiments for the same systems. We revealed that this difference is not due to the arginine-arginine pairing, but is due to the semiflexibility effect associated with the different contour length from CH 2-N group to the end of the side arginine or lysine segment in spacers.

AB - New peptide dendrimer with Lys-2Arg repeating units was recently studied experimentally by NMR (RSC Advances, 2019, 9, 18018) and tested as gene carrier successfully (Int. J. Mol. Sci., 2020, 21, 3138). The unusual slowing down of the orientational mobility of 2Arg spacers in this dendrimer was revealed. It has been suggested that this unexpected behavior is caused by the Arg-Arg pairing effect in water, which leads to entanglements between dendrimer branches. In this paper, we determine the reason for this slowing down using atomistic molecular dynamics simulation of this dendrimer. We present that the structural properties of Lys-2Arg dendrimer are close to those of the Lys-2Lys dendrimer at all temperatures (Polymers, 2020, 12, 1657). However, the orientational mobility of the H-H vector in CH 2-N groups of 2Arg spacers in Lys-2Arg dendrimer is significantly slower than the mobility of the same vector in the Lys-2Lys dendrimer. This result is in agreement with the recent NMR experiments for the same systems. We revealed that this difference is not due to the arginine-arginine pairing, but is due to the semiflexibility effect associated with the different contour length from CH 2-N group to the end of the side arginine or lysine segment in spacers.

KW - peptide dendrimer

KW - COMPUTER SIMULATION

KW - Molecular dynamics

KW - Zeta Potential

KW - NMR

KW - spin-lattice relaxation time

KW - Computer simulation

KW - Molecular dynamics

KW - NMR

KW - Peptide dendrimer

KW - Spin-lattice relaxation time

KW - Zeta potential

UR - http://www.scopus.com/inward/record.url?scp=85098326765&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/afcb19ae-b921-3543-915a-8382cfb75013/

U2 - 10.3390/ijms21249749

DO - 10.3390/ijms21249749

M3 - Article

C2 - 33371242

VL - 21

SP - 1

EP - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 24

M1 - 9749

ER -