Novel Peptides Bind Elusive Therapeutic Target Critical to HIV Lifecycle

At a Glance

Researchers at Colorado State University have developed cyclic peptides with high affinity binding to the HIV-1 Trans-activation response (TAR) element RNA.  The TAR element RNA is highly resistant to mutation and has been validated as a drug target in the treatment for HIV.   Structural analysis and experimentation revealed these cyclic proteins exhibited extraordinarily tight TAR affinity and impaired TAR binding to the Tat peptide (attenuating Tat dependent transcription).

Background

There is no cure for HIV/AIDS, but there are many drugs available that help control virus activity and slow disease progression. The current form of antiretroviral therapy (ART) recommended for every infected individual consists of a concurrent regimen of three medications from any two classes of drugs that specifically target HIV progression. This combination therapy reduces the risk of creating drug-resistant strains of HIV as each class of drug blocks viral replication and disease progression in a different way. However, drug resistance remains an ongoing issue due to the high rate of mutation by the HIV virus.

The HIV-1 TAR element RNA is comprised of a conserved, bulge stem-loop that is highly resistant to mutation, and has been validated as a drug target. The TAR plays a critical role in facilitating pro-viral transcription and blocking apoptosis of the infected host cell – which is imperative to the continuation of the HIV life cycle. Although it is well known that TAR is a target worth pursuing, it has been difficult to discover or develop small molecules or peptides with sufficient affinity and selectivity to warrant further pharmaceutical development. New targets that are also resistant to mutation (such as the HIV-1 TAR element RNA) are needed to improve long term therapeutic outcomes.

Benefits

  • HIV-1 TAR has been validated as a target for for antiretroviral therapeutic use
  • HIV-1 TAR is highly conserved and highly resistant to mutation
  • HIV-1 TAR has been refractory to the discovery of peptides or small molecules by competitors, as affinity and selectivity is a crucial parameter for drug development
  • Cyclic peptides are highly selective to HIV-1 TAR, and bind with high affinity
Last Updated: April 2022
Diagram/Illustration of cyclic peptides
Opportunity

Available for Licensing

Inventors

Brian Mcnaughton
David W Crawford

Reference Number
17-024
Licensing Manager

Steve Foster
Steve.Foster@colostate.edu
970-491-7100