Targeted protein degradation has recently gained widespread interest as both a novel therapeutic strategy and a useful tool in biomedical research. Targeted protein degraders are often sub-stoichiometric and do not require strong binding affinity for their targets, enabling access to previously inaccessible targets. Proteolysis-targeting chimeras (PROTACs) are one class of targeted protein degraders that promote degradation by recruiting a target protein to an E3-ligase complex via a heterobifunctional molecule. The modular nature of PROTACs allows for their rational design and systematic optimization. Here we suggest resources and methodologies for developing PROTAC degraders for researchers that may be new to the field. © 2022 Wiley Periodicals LLC.

Retention in healthcare and health behavior remains a critical issue, contributing to inequitable distribution of intervention benefits. In diseases such as HIV, where half of the new infections occur among racial and sexual minorities, it is important that interventions do not enlarge pre-existing health disparities. To effectively combat this public health issue, it is crucial that we quantify the magnitude of racial/ethnic disparity in retention. Further, there is a need to identify mediating factors to this relationship to inform equitable intervention design. In the present study, we assess the racial/ethnic disparity in retention in a peer-led online behavioral intervention to increase HIV self-testing behavior and identify explanatory factors. The research used data collected from the Harnessing Online Peer Education (HOPE) HIV Study that included 899 primarily African American and Latinx men who have sex with men (MSM) in the United States. Results show that African American participants had higher lost-to-follow-up rates at 12-week follow-up compared to Latinx participants (11.1% and 5.8% respectively, Odds Ratio = 2.18, 95% confidence interval: 1.12 - 4.11, p = 0.02), which is substantially mediated by participants' self-rated health score (14.1% of the variation in the African American v.s. Latinx difference in lost-follow-up, p = 0.006). Thus, how MSM perceive their health may play an important role in their retention in HIV-related behavioral intervention programs and its racial/ethnic disparity.