Bioorganic synthesis of a recombinant HIV-1 fusion inhibitor, SC35EK, with an N-terminal pyroglutamate capping group

Abstract

The bioorganic synthesis of an end-capped anti-HIV peptide from a recombinant protein was investigated. Cyanogen bromide-mediated cleavage of two Met-Gln sites across the target anti-HIV sequence generated an HIV-1 fusion inhibitor (SC35EK) analog bearing an N-terminal pyroglutamate (pGlu) residue and a C-terminal homoserine lactone (Hsl) residue. The end-capped peptide, pGlu-SC35EK-Hsl, had similar bioactivity and biophysical properties to the parent peptide, and an improved resistance to peptidase-mediated degradation was observed compared with the non-end-capped peptide obtained using standard recombinant technology.

Stereoselective Construction of Spiro(butyrolactonepyrrolidines) by Highly Efficient Copper(I)/TF‐BiphamPhos‐Catalyzed Asymmetric 1,3‐Dipolar Cycloaddition

“…Typical examples include cephalotaxine,2 stemmonamine,3 and spirotryprostatins A and B4 (Figure 1). 5 Homoserine lactone derivatives have also attracted considerable attention due to their biological activity profile 6. Typical examples are the acyl homoserine lactones (AHLs), which are important intercellular signaling molecules in many Gram‐negative bacteria and are responsible for bacterial quorum sensing (Figure 1).…”

“…[5] Homoserine lactone derivatives have also attracted considerable attention due to their biological activity profile. [6] Typical examples are the acyl homoserine lactones (AHLs), which are important intercellular signaling molecules in many Gram-negative bacteria and are responsible for bacterial quorum sensing ( Figure 1). [7] Therefore, combining the two classes of biologically active core structure through a unique spiro-quaternary stereogenic carbon may introduce some unprecedented benefits to drug discovery and is expected to find valuable applications in medicinal chemistry.The spirocyclic pyrrolidine skeleton has potential as a key motif for the development of compounds leading to medicinal agents.…”

Therapeutic and prevention strategies against human enterovirus 71 infection

“…A major disadvantage of peptides is their low bioavailability due to their rapid degradation in the gastrointestinal system. To circumvent this issue, new formulations such as the D-isomer peptide [64] , addition of N-terminal pyroglutamate and C-terminal homoserine lactone to the peptide, are being developed to improve the resistance to peptidase [66] . Attachment and entry inhibitors stop the virus from entering cells, and therefore may be useful as prophylactic agents.…”