Stability in human serum and plasma of the HIV peptide drug candidate CIGB‐210 and improved variants.
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| Title: | Stability in human serum and plasma of the HIV peptide drug candidate CIGB‐210 and improved variants. |
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| Authors: | Duarte, Carlos A.1 (AUTHOR) carlos.duarte@cigb.edu.cu, Cabrales, Ania2 (AUTHOR), Echevarría, Reina1 (AUTHOR), Paneque, Taimí1 (AUTHOR), Ramírez, Anna C.1 (AUTHOR), Casillas, Dionne1 (AUTHOR), Sobrino‐Iglesias, Xeila2 (AUTHOR), Garay, Hilda2 (AUTHOR), Besada, Vladimir2 (AUTHOR), Fernández‐Ortega, Celia1 (AUTHOR) |
| Source: | Biotechnology & Applied Biochemistry. Feb2025, Vol. 72 Issue 1, p187-195. 9p. |
| Subjects: | Peptides, Cytoplasmic filaments, Plasma stability, Liquid chromatography, Anti-HIV agents |
| Abstract: | The peptide CIGB‐210 inhibits HIV replication, inducing a rearrangement of vimentin intermediate filaments. The assessment of the in vitro serum and plasma stability of this peptide is important to develop an optimal pharmacological formulation. A half‐life of 17.68 ± 0.59 min was calculated for CIGB‐210 in human serum by reverse‐phase high‐performance liquid chromatography (HPLC) and mass spectrometry (MS). Eight metabolites of CIGB‐210 were identified with this methodology, all of them lacking the N‐terminal moiety. A previously developed CIGB‐210 in‐house competitive ELISA was used to compare the stability of CIGB‐210 derivatives containing either D‐amino acids, acetylation at the N‐terminus, or both modifications. The half‐life of CIGB‐210 in serum was five times higher when measured by ELISA than by HPLC/MS, and twice higher in plasma as compared to serum. The substitution of D‐asparagine on position 6 doubled the half‐life, while D‐amino acids on positions 8 and 9 did not improve the stability. The acetylation of the N‐terminus resulted in a 24‐fold more stable peptide in plasma. The positive effect of N‐terminal acetylation on CIGB‐210 serum stability was confirmed by the HPLC/MS method, as the half‐life of the peptide was not reached after 2 h of incubation, which represents more than a 6.8‐fold increase in the half‐life with respect to the original peptide. [ABSTRACT FROM AUTHOR] |
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| Database: | Engineering Source |
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| Abstract: | The peptide CIGB‐210 inhibits HIV replication, inducing a rearrangement of vimentin intermediate filaments. The assessment of the in vitro serum and plasma stability of this peptide is important to develop an optimal pharmacological formulation. A half‐life of 17.68 ± 0.59 min was calculated for CIGB‐210 in human serum by reverse‐phase high‐performance liquid chromatography (HPLC) and mass spectrometry (MS). Eight metabolites of CIGB‐210 were identified with this methodology, all of them lacking the N‐terminal moiety. A previously developed CIGB‐210 in‐house competitive ELISA was used to compare the stability of CIGB‐210 derivatives containing either D‐amino acids, acetylation at the N‐terminus, or both modifications. The half‐life of CIGB‐210 in serum was five times higher when measured by ELISA than by HPLC/MS, and twice higher in plasma as compared to serum. The substitution of D‐asparagine on position 6 doubled the half‐life, while D‐amino acids on positions 8 and 9 did not improve the stability. The acetylation of the N‐terminus resulted in a 24‐fold more stable peptide in plasma. The positive effect of N‐terminal acetylation on CIGB‐210 serum stability was confirmed by the HPLC/MS method, as the half‐life of the peptide was not reached after 2 h of incubation, which represents more than a 6.8‐fold increase in the half‐life with respect to the original peptide. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 08854513 |
| DOI: | 10.1002/bab.2655 |
