Abstract
Membrane interaction constitutes to be an essential parameter in the mode of action of entities such as proteins, as well as cell-penetrating and antimicrobial peptides, resulting in noninvasive or lytic activities depending on the membrane compositions and interactions. Recently, a nanobody able to interact with the top priority, multidrug-resistant bacterial pathogen Acinetobacter baumannii was discovered, although binding took place with fixed cells only. To potentially overcome this limitation, linear peptides corresponding to the complementarity-determining regions (CDR) were synthesized and fluorescently labeled. Microscopy data indicated clear membrane interactions of the CDR3 sequence with living A. baumannii cells, indicating both the importance of the CDR3 as part of the parent nanobody paratope and the improved binding ability and thus avoiding the need for permeabilization of the cells. In addition, cyclization of the peptide with an additionally introduced rigidifying 1,2,3-triazole bridge retains its binding ability while proteolytically protecting the peptide. Overall, this study resulted in the discovery of novel peptides binding a multidrug-resistant pathogen.
| Original language | English |
|---|---|
| Pages (from-to) | 1234-1243 |
| Number of pages | 10 |
| Journal | Bioconjugate Chemistry |
| Volume | 34 |
| Issue number | 7 |
| Early online date | 7 Jul 2023 |
| DOIs | |
| Publication status | Published - 19 Jul 2023 |
Bibliographical note
Funding Information:K.V.h. and S.B. thank the Research Foundation–Flanders (FWO Vlaanderen) for providing a PhD fellowship to K.V.h (FWOTM931). K.V.h., M.M., and S.B. thank the Research Council of the Vrije Universiteit Brussel for financial support through the spearhead (SRP50) program. A.B., C.V.d.H., and H.R. thank the Research Foundation–Flanders (FWO Vlaanderen) for providing a PhD SB fellowship to A.B. (File number 77258). C.V.d.H. acknowledges the Vlaams Instituut voor Biotechnologie (VIB) for their support. E.P. and J.S. acknowledge the support and the use of resources of Instruct-ERIC, part of the European Strategy Forum on Research Infrastructures (ESFRI), and the Research Foundation–Flanders (FWO) for their support to the Nanobody discovery and Nele Buys for the technical assistance during Nanobody discovery.
Funding Information:
K.V.h. and S.B. thank the Research Foundation-Flanders (FWO Vlaanderen) for providing a PhD fellowship to K.V.h (FWOTM931). K.V.h., M.M., and S.B. thank the Research Council of the Vrije Universiteit Brussel for financial support through the spearhead (SRP50) program. A.B., C.V.d.H., and H.R. thank the Research Foundation-Flanders (FWO Vlaanderen) for providing a PhD SB fellowship to A.B. (File number 77258). C.V.d.H. acknowledges the Vlaams Instituut voor Biotechnologie (VIB) for their support. E.P. and J.S. acknowledge the support and the use of resources of Instruct-ERIC, part of the European Strategy Forum on Research Infrastructures (ESFRI), and the Research Foundation-Flanders (FWO) for their support to the Nanobody discovery and Nele Buys for the technical assistance during Nanobody discovery.
Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.
Copyright:
Copyright 2023 Elsevier B.V., All rights reserved.