Title: Optimization of the pharmacophore that binds the CD4 pocket at residue x improves potency of synthesized cPT
In 2020, approximately 37.6 million people worldwide had ongoing HIV infections. Currently, there are some drugs on the market to slow down the spread of HIV, however there is no cure or vaccine. Therefore, it is imperative to work towards a drug which could prevent infection in the first place. Some of the current drugs on the market focus on inhibiting the process of viral replication within the cell by targeting enzymes such as integrase and protease. The gp120 trimer complex on the viral envelope on HIV is of particular interest as this spike attaches to host cells to allow entry of the viral proteins and genetic material. The Chaiken lab group focuses on developing a peptide to bind to the CD4 Phe 43 pocket to prevent viral entry. The cyclic peptide triazole of N8 is the lead candidate to bind to the pocket. This summer, I focused on the synthesis of N8 and measured the compound’s ability to bind to the targeted proteins of YU2 gp120. On the N8 compound reside three potential moieties for modification: the triazole, tryptophan and isoleucine groups. Moving forward, various modifications of these groups may improve N8’s binding ability to its target gp120 complex.
In 2020, approximately 37.6 million people worldwide had ongoing HIV infections. Currently, there are some drugs on the market to slow down the spread of HIV, however there is no cure or vaccine. Therefore, it is imperative to work towards a drug which could prevent infection in the first place. Some of the current drugs on the market focus on inhibiting the process of viral replication within the cell by targeting enzymes such as integrase and protease. The gp120 trimer complex on the viral envelope on HIV is of particular interest as this spike attaches to host cells to allow entry of the viral proteins and genetic material. The Chaiken lab group focuses on developing a peptide to bind to the CD4 Phe 43 pocket to prevent viral entry. The cyclic peptide triazole of N8 is the lead candidate to bind to the pocket. This summer, I focused on the synthesis of N8 and measured the compound’s ability to bind to the targeted proteins of YU2 gp120. On the N8 compound reside three potential moieties for modification: the triazole, tryptophan and isoleucine groups. Moving forward, various modifications of these groups may improve N8’s binding ability to its target gp120 complex.