Discovery of Selective Cyclic d-Sulfopeptide Ligands of the Chemokine CCL22 via Mirror-Image mRNA Display with Genetic Reprogramming.

Chemokines are small proteins involved in recruiting leukocytes to sites of inflammation via interactions with specific cell surface receptors. CCL22 is a chemokine known to play a critical role in inflammatory diseases such as atopic dermatitis and asthma; inhibition of this chemokine therefore represents an attractive therapeutic strategy. Herein, we describe the discovery of cyclic d-sulfopeptide inhibitors of CCL22 identified through mirror-image mRNA display with genetic reprogramming.

Chemokine Receptor N-Terminus Charge Dictates Reliance on Post-Translational Modifications for Effective Ligand Capture and Following Boosting by Defense Peptides.

The chemokine receptors CCR1 and CCR5 display overlapping expression patterns and ligand dependency. Here we find that ligand activation of CCR5, not CCR1, is dependent on N-terminal receptor O-glycosylation. Release from O-glycosylation dependency is obtained by increasing CCR5 N-terminus acidity to the level of CCR1.

CXCL12 chemokine dimer signaling modulates acute myelogenous leukemia cell migration through altered receptor internalization.

Acute myeloid leukemia (AML) is a malignancy of immature myeloid blast cells with stem-like and chemoresistant cells being retained in the bone marrow through CXCL12-CXCR4 signaling. Current CXCR4 inhibitors mobilize AML cells into the bloodstream where they become more chemosensitive have failed to improve patient survival, likely reflecting persistent receptor localization on target cells. Here we characterize the signaling properties of CXCL12-locked dimer (CXCL12-LD), a bioengineered variant of the dimeric CXCL12 structure.

Applying Communication Science to Substance Use Prevention Messaging.

Despite a wealth of evidence-based messaging on youth alcohol and drug prevention, there remains a dearth of research on how to construct and deliver these messages effectively. Communication science is useful for increasing the efficacy of these messages in reducing substance use risk among youth. This study explores the perspectives of youth and youth-serving providers to identify theory-informed substance use prevention messages and strategies and how the content and delivery of prevention messages evolved during the COVID-19 pandemic.

Structural basis for selectivity and antagonism in extracellular GPCR-nanobodies.

G protein-coupled receptors (GPCRs) are pivotal therapeutic targets, but their complex structure poses challenges for effective drug design. Nanobodies, or single-domain antibodies, have emerged as a promising therapeutic strategy to target GPCRs, offering advantages over traditional small molecules and antibodies. However, an incomplete understanding of the structural features enabling GPCR-nanobody interactions has limited their development.