Therapeutic Potential of Trp-Rich Engineered Amphiphiles by Single Hydrophobic Amino Acid End-Tagging

The aim of this paper is to explore the mechanism of the change in oestrogenic activity of PCBs molecules before and after modification by designing new PCBs derivatives in combination with molecular docking techniques through the constructed model of oestrogenic activity of PCBs molecules. We found that the weakened hydrophobic interaction between the hydrophobic amino acid residues and hydrophobic substituents at the binding site of PCB derivatives and human oestrogen receptor alpha (hERα) was the main reason for the weakened binding force and reduced anti-oestrogenic activity. It was consistent with the information that the hydrophobic field displayed by the 3D contour maps in the constructed oestrogen activity CoMSIA model was one of the main influencing force fields. The hydrophobic interaction between PCB derivatives and oestrogen-active receptors was negatively correlated with the average distance between hydrophobic substituents and hydrophobic amino acid residues at the hERα-binding site, and positively correlated with the number of hydrophobic amino acid residues. In other words, the smaller the average distance between the hydrophobic amino acid residues at the binding sites between the two and the more the number of them, and the stronger the oestrogen activity expression degree of PCBS derivative molecules. Therefore, hydrophobic interactions between PCB derivatives and the oestrogen receptor can be reduced by altering the microenvironmental conditions in humans. This reduces the ability of PCB derivatives to bind to the oestrogen receptor and can effectively modulate the risk of residual PCB derivatives to produce oestrogenic activity in humans.

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Poly(hydrophobic amino acid)-Based Self-Adjuvanting Nanoparticles for Group A Streptococcus Vaccine Delivery

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.0c01660 ◽

2021 ◽

Author(s):

Armira Azuar ◽

Zhuoqing Li ◽

Mohini A. Shibu ◽

Lili Zhao ◽

Yacheng Luo ◽

...

Keyword(s):

Amino Acid ◽

Group A Streptococcus ◽

Vaccine Delivery ◽

Hydrophobic Amino Acid ◽

Group A

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The central hydrophobic domain of the bovine papillomavirus E5 transforming protein can be functionally replaced by many hydrophobic amino acid sequences containing a glutamine.

Journal of Virology ◽

10.1128/jvi.66.1.505-511.1992 ◽

1992 ◽

Vol 66 (1) ◽

pp. 505-511 ◽

Cited By ~ 28

Author(s):

R Kulke ◽

B H Horwitz ◽

T Zibello ◽

D DiMaio

Keyword(s):

Amino Acid ◽

Amino Acid Sequences ◽

Bovine Papillomavirus ◽

Hydrophobic Amino Acid ◽

Hydrophobic Domain

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Stabilization of secondary structure elements by specific combinations of hydrophilic and hydrophobic amino acid residues is more important for proteins encoded by GC-poor genes

Biochimie ◽

10.1016/j.biochi.2012.08.008 ◽

2012 ◽

Vol 94 (12) ◽

pp. 2706-2715 ◽

Cited By ~ 12

Author(s):

Vladislav Victorovich Khrustalev ◽

Eugene Victorovich Barkovsky

Keyword(s):

Amino Acid ◽

Secondary Structure ◽

Amino Acid Residues ◽

Hydrophobic Amino Acid

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The anti-leishmanial activity of dipeptide esters on Leishmania amazonensis amastigotes

Parasitology ◽

10.1017/s0031182000061205 ◽

1990 ◽

Vol 100 (2) ◽

pp. 201-207 ◽

Cited By ~ 6

Author(s):

C. Ramazeilles ◽

L. Juliano ◽

J. R. Chagas ◽

M. Rabinovitch

Keyword(s):

Amino Acid ◽

Methyl Esters ◽

Leishmania Amazonensis ◽

Amino Acid Esters ◽

Cysteine Proteinases ◽

Hydrophobic Amino Acid ◽

Structure Activity ◽

Reduction Assay ◽

Mtt Reduction ◽

Acid Esters

SUMMARYL-Amino acid esters, such as L-Leu-OMe, kill Leishmania amazonensis amastigotes by a mechanism which appears to involve ester hydrolysis by cysteine proteinases located in the parasite megasomes. We have examined the killing of isolated amastigotes by L-dipeptide esters and derived some structure-activity correlations. Toxicity of the compounds for the parasites was measured by a tetrazolium (MTT) reduction assay. The results show that active dipeptide esters contained at least I hydrophobic amino acid (Leu, Ile, Val, Phe or Trp). The activity of homodipeptide methyl esters depended on the nature of the amino acid, as indicated by the following series: Phe-Phe-OMe < Val-Val-OMe < Leu-Leu-OMe < Trp-Trp-OMe < Ile-Ile-OMe. The nature of the amino acids in Leu-X-OMe and X-Leu-OMe was relatively unimportant when X was Phe, Trp or Val. However, when X was Ala or Gly, Leu-X-OMe was several-fold more active than X-Leu-OMe.

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