Enantiomeric and Diastereomeric Self-Assembled Multivalent Nanostructures: Understanding the Effects of Chirality on Binding to Polyanionic Heparin and DNA

TY - JOUR

T1 - Enantiomeric and Diastereomeric Self-Assembled Multivalent Nanostructures

T2 - Understanding the Effects of Chirality on Binding to Polyanionic Heparin and DNA

AU - Thornalley, Kiri A.

AU - Laurini, Erik

AU - Pricl, Sabrina

AU - Smith, David K.

N1 - © 2018 Wiley‐VCH Verlag. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2018/7/9

Y1 - 2018/7/9

N2 - A family of four self-assembling lipopeptides containing Ala-Lys peptides attached to a C16 aliphatic chain were synthesised. These compounds form two enantiomeric pairs that bear a diastereomeric relationship to one another (C16-l-Ala-l-Lys/C16-d-Ala-d-Lys) and (C16-d-Ala-l-Lys/C16-l-Ala-d-Lys). These diastereomeric pairs have very different critical micelle concentrations (CMCs). The self-assembled multivalent (SAMul) systems bind biological polyanions as a result of the cationic lysine groups on their surfaces. For heparin binding, there was no significant enantioselectivity, but there was a binding preference for the diastereomeric assemblies with lower CMCs. Conversely, for DNA binding, there was significant enantioselectivity for systems displaying d-lysine ligands, with a further slight preference for attachment to l-alanine, with the CMC being irrelevant.

AB - A family of four self-assembling lipopeptides containing Ala-Lys peptides attached to a C16 aliphatic chain were synthesised. These compounds form two enantiomeric pairs that bear a diastereomeric relationship to one another (C16-l-Ala-l-Lys/C16-d-Ala-d-Lys) and (C16-d-Ala-l-Lys/C16-l-Ala-d-Lys). These diastereomeric pairs have very different critical micelle concentrations (CMCs). The self-assembled multivalent (SAMul) systems bind biological polyanions as a result of the cationic lysine groups on their surfaces. For heparin binding, there was no significant enantioselectivity, but there was a binding preference for the diastereomeric assemblies with lower CMCs. Conversely, for DNA binding, there was significant enantioselectivity for systems displaying d-lysine ligands, with a further slight preference for attachment to l-alanine, with the CMC being irrelevant.

KW - DNA

KW - heparin

KW - multivalency

KW - self-assembly

KW - supramolecular chemistry

UR - http://www.scopus.com/inward/record.url?scp=85049581808&partnerID=8YFLogxK

U2 - 10.1002/anie.201803298

DO - 10.1002/anie.201803298

M3 - Article

AN - SCOPUS:85049581808

SN - 1433-7851

VL - 57

SP - 8530

EP - 8534

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 28

ER -