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Alternative Structure-Function Insight Into Angiotensin II Positions 3 and 4 Based on Investigations of Analogues Containing Unconventional Amino Acid Derivatives
Version 1
: Received: 7 June 2024 / Approved: 10 June 2024 / Online: 10 June 2024 (11:57:09 CEST)
How to cite:
Nakaie, C. R.; Barros, A. D. J. Alternative Structure-Function Insight Into Angiotensin II Positions 3 and 4 Based on Investigations of Analogues Containing Unconventional Amino Acid Derivatives. Preprints2024, 2024060568. https://doi.org/10.20944/preprints202406.0568.v1
Nakaie, C. R.; Barros, A. D. J. Alternative Structure-Function Insight Into Angiotensin II Positions 3 and 4 Based on Investigations of Analogues Containing Unconventional Amino Acid Derivatives. Preprints 2024, 2024060568. https://doi.org/10.20944/preprints202406.0568.v1
Nakaie, C. R.; Barros, A. D. J. Alternative Structure-Function Insight Into Angiotensin II Positions 3 and 4 Based on Investigations of Analogues Containing Unconventional Amino Acid Derivatives. Preprints2024, 2024060568. https://doi.org/10.20944/preprints202406.0568.v1
APA Style
Nakaie, C. R., & Barros, A. D. J. (2024). Alternative Structure-Function Insight Into Angiotensin II Positions 3 and 4 Based on Investigations of Analogues Containing Unconventional Amino Acid Derivatives. Preprints. https://doi.org/10.20944/preprints202406.0568.v1
Chicago/Turabian Style
Nakaie, C. R. and Alexandre De Jesus Barros. 2024 "Alternative Structure-Function Insight Into Angiotensin II Positions 3 and 4 Based on Investigations of Analogues Containing Unconventional Amino Acid Derivatives" Preprints. https://doi.org/10.20944/preprints202406.0568.v1
Abstract
A novel investigation into the structure-function relationship was undertaken to enhance understanding of the mechanism of action of the vasoactive peptide angiotensin II (AngII) using unconventional substitutions such as AIB (α-aminobutyric acid), CHA (cyclohexylalanine acid), IAP (isonipecotic acid), TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amine-4-carboxylic acid) at position 3, and DMT (2,6-dimethyl-Tyrosine) at position 4. Biological potency assays were conducted on guinea pig ileum, and structural features were analyzed using circular dichroism (CD) and molecular dynamics (MD).
CHA3-AngII and AIB3-AngII analogs retained some agonistic activity, whereas IAP3-AngII and TOAC3-AngII derivatives were inactive. CD results indicated low conformational flexibility for AIB3-AngII and CHA3-AngII, and greater conformational restrictions for IAP3-AngII and TOAC3-AngII, consistent with computational modeling analyses. DMT4-AngII exhibited significant agonistic activity compared to the inactive Phe4AngII. Molecular modeling suggested a potential interaction between the hydroxyl group of Tyr4 and the amide bond between positions 7 and 8. AngII showed greater conformational restriction compared to DMT4-AngII and Phe4-AngII, underscoring the importance of tyrosine at position 4.
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
