Design, Structure-Activity Relationships, and Computational Modeling Studies of a Series of α-Helix Biased, Ultra-Short Glucagon-like Peptide-1 Receptor Agonists.

A systematic structure-activity and computational modeling analysis of a series of glucagon-like peptide-1 receptor (GLP-1R) agonists based upon an ultra-short GLP-1 peptide, H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Bip-Bip-NH2, was conducted. This highly potent 11-mer peptide led to a deeper understanding of the α-helical bias of strategic α-methylation within the linear parent template as well as optimization of GLP-1R agonist potency by 1000-fold. These data were correlated with previously reported co-structures of both full-length GLP-1 analogs and progenitor N-terminal GLP-1 fragment analogs related to such ultra-short GLP-1R agonist peptides.

THE STING AGONIST VB-85247 INDUCES DURABLE ANTITUMOR IMMUNE RESPONSES BY INTRAVESICAL ADMINISTRATION IN A NON-MUSCLE INVASIVE BLADDER CANCER.

Bacillus Calmette-Guerin (BCG) is the current standard of care for non-muscle invasive bladder cancer (NMIBC), but recurrence is common. Additional therapeutic options are a major unmet medical need for treating unresponsive patients. Stimulator of Interferon Genes (STING) plays a central role in mounting innate and adaptive immune responses to tumor cells, and activation of STING is a promising immunotherapeutic approach.

Decision-Making During Asynchronous Electives: Insights From Emergency Medicine-Bound Medical Students.

Introduction While asynchronous learning is gaining popularity, little is known about learners' decisions regarding compliance with assigned asynchronous material. We sought to explore how medical students make decisions about the use of their time when engaging in asynchronous learning during the residency interview season.  Methods After implementing a four-week blended elective for emergency medicine-bound fourth-year medical students, we conducted a mixed methods study with an explanatory sequential design.

Recent applications of computational methods to allosteric drug discovery.

Interest in exploiting allosteric sites for the development of new therapeutics has grown considerably over the last two decades. The chief driving force behind the interest in allostery for drug discovery stems from the fact that in comparison to orthosteric sites, allosteric sites are less conserved across a protein family, thereby offering greater opportunity for selectivity and ultimately tolerability. While there is significant overlap between structure-based drug design for orthosteric and allosteric sites, allosteric sites offer additional challenges mostly involving the need to better understand protein flexibility and its relationship to protein function.

Is it worth it? A qualitative analysis of the impact of medical education fellowships on careers.

Objectives: Medical education fellowships provide training in teaching, assessment, educational program administration, and scholarship. The longitudinal impact of this training is unknown. The objective of this study was to explore the impact of medical education fellowships on the careers of graduates.