Systemically-delivered formulations may be further developed for additional cases of ACV-resistant HSV-1 infections. Helix stabilization by cross-linking had been shown previously to increase. These peptides can be prepared into a solution for topical administration and may be used alone or in addition to ACV. The stapled peptides are protein fragments chemically locked into an -helical shape. Successful blockade of HSV-1 DNA synthesis and HSV-1 infection by the peptide has been shown in vitro. Without PF association, the polymerase rapidly dissociates from the DNA template, preventing productive genome replication. This stabilized peptide mimics the C-terminal α-helix of HSV-1 DNA polymerase to block interaction between the polymerase and the HSV-1 processivity factor (PF). Two ,-disubstituted residues bearing olefin side chains of varying lengths are introduced into the peptide -helix, followed by a ruthenium-catalysed ring-closing metathesis reaction to form the staple across one or two -helical turns (Fig. The all-carbon scaffold stabilizes the -helical structure, enhances the interaction between the peptide molecule and the protein, and the peptide can pass through the cell membrane and is not easily hydrolyzed. In this review, we summarize the broad aspects of peptide stapling for chemistry, biophysics, and biological applications and specifically highlight the. The hydrocarbon stapling technique combines two -helix stabilisation strategies, namely ,-disubstitution and macrocyclic bridge formation. Stapled peptide is a full-carbon scaffold with an -helical structure. spacer to isolate the modification from the core of the stapled peptide. Scientists at the University of Pennsylvania have developed a stapled α-helical peptide for the treatment of HK. Stapled helical peptides, by adopting a preformed, stable -helical conformation, exhibit improved proteolytic stability and membrane permeability compared to linear bioactive peptides. to the N-terminus of stapled peptides are fluorescein, which can be used for. Modern day medicinal chemistry increasingly relies on synthetic biomolecules designed and produced using biotechnology.
While this drug remains effective against oral and genital herpes, there is an emergence of ACV-resistant HK infections caused by mutations in the HSV-1 TK gene, and a need for therapies against alternative HSV-1 targets. The gold standard for treatment of HK is acyclovir (ACV), a drug that targets viral thymidine kinase (TK). Following initial infection, recurrent activation along the ophthalmic branch of the cranial trigeminal nerve can lead to Herpes Ocular Keratitis (HK), the leading cause of corneal blindness in the US and in the world.
Nearly two thirds of the world population is infected with Herpes simplex virus-1 (HSV-1).
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