Nemzeti Gyógyszerkutatási és Fejlesztési Laboratórium (PharmaLab)(RRF-2.3.1-21-2022-00015)
Támogató: NKFIH
Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009)
Támogató: EFOP-VEKOP
Szakterületek:
Tudomány
The modification of well‐known β ‐peptide helices has been achieved by the application
of N‐terminal betaine conjugation. The 3D self‐organization of oligomers formed by
[1 S ,2 S ]‐2‐aminocyclopentanecarboxylic acid (ACPC), [1 R ,2 R ]‐2‐aminocyclohexanecarboxylic
acid (ACHC), and an alternating heterochiral homooligomer of [1 S ,2 S ]‐ACPC and
[1 R ,2 R ]‐ACPC was studied. Results of NMR, ECD, FT‐IR, and molecular modeling showed
that for [1 S ,2 S ]‐ACPC pentamer ( 1 ), the betaine conjugation did not affect the
folding to an H12 helix. In contrast, for the [1 R ,2 R ]‐ACHC tetramer ( 2 ) betaine
conjugation notably influenced the folding, and an H14 helix was observed instead
of the expected H10 helix. In addition, this is the first observation of self‐association
for an H12 helix forming β ‐peptide. Based on TEM images, this association leads to
vesicle morphologies. For the alternating heterochiral homooligomer [1 S ,2 S ]‐ACPC
and the [1 R ,2 R ]‐ACPC pentamer ( 3 ), betaine conjugation enhances the solubility
of the system. Moreover, the formation of an expected E‐strand can be anticipated,
since self‐association was found in the form of a fibrin net‐like structure in TEM
images. Betaine conjugates described herein open a new area of bioactive peptide foldamer
construction, since the introduced quaternary charges may lead to important receptor‐ligand
interactions, while potential material science applications can also be realized.
