Cyclic Peptides that Govern Signal Transduction Pathways: From Prokaryotes to Multi-Cellular Organisms.

Cyclic peptide scaffolds are key components of signal transduction pathways in both prokaryotic and eukaryotic organisms since they act as chemical messengers that activate or inhibit specific cognate receptors. In prokaryotic organisms these peptides are utilized in non-essential pathways, such as quorum sensing, that are responsible for virulence and pathogenicity. In the more evolved eukaryotic systems, cyclic peptide hormones play a key role in the regulation of the overall function of multicellular organisms, mainly through the endocrine system. This review will highlight several prokaryote and eukaryote systems that use cyclic peptides as their primary signals and the potential associated with utilizing these scaffolds for the discovery of novel therapeutics for a wide range of diseases and illnesses.

Patient perceptions of treatment-free remission in chronic myeloid leukemia.

Around half of patients with chronic myeloid leukemia (CML) who achieve a stable deep molecular response would remain in treatment-free remission (TFR) if their tyrosine kinase inhibitors (TKIs) were stopped. TFR is increasingly becoming a goal of treatment. Eighty-seven patients answered a survey exploring patient perceptions of TFR, incorporating CML-specific factors (disease history, treatment toxicity, and adherence) and questions concerning health beliefs. 81% of participants (95% CI: 72%-89%) indicated that they would be willing to attempt TFR. No demographic or CML-related variable in the survey was significantly associated with willingness. In qualitative analysis, the commonest motivations for TFR included TKI toxicity (n = 26) and convenience (n = 18). The leading reason for reluctance was fear of consequences of stopping TKI (n = 16). Reluctance was often associated with needs for additional information or incomplete understanding of the current data. Understanding patient motivations and concerns is important if TFR is to become a part of CML management.

Structure-Activity Relationships of the Competence Stimulating Peptides (CSPs) in Streptococcus pneumoniae Reveal Motifs Critical for Intra-group and Cross-group ComD Receptor Activation.

Streptococcus pneumoniae is a highly recombinogenic human pathogen that utilizes the competence stimulating peptide (CSP)-based quorum sensing (QS) circuitry to acquire antibiotic resistance genes from the environment and initiate its attack on the human host. Modulation of QS in this bacterium, either inhibition or activation, can therefore be used to attenuate S. pneumoniae infectivity and slow down pneumococcal resistance development. In this study, we set to determine the molecular mechanism that drives CSP:receptor binding and identify CSP-based QS modulators with distinct activity profiles. To this end, we conducted systematic replacement of the amino acid residues in the two major CSP signals (CSP1 and CSP2) and assessed the ability of the mutated analogs to modulate QS against both cognate and noncognate ComD receptors. We then evaluated the overall 3D structures of these analogs using circular dichroism (CD) to correlate between the structure and function of these peptides. Our CD analysis revealed a strong correlation between α-helicity and bioactivity for both specificity groups (CSP1 and CSP2). Furthermore, we identified the first pan-group QS activator and the most potent group-II QS inhibitor to date. These chemical probes can be used to study the role of QS in S. pneumoniae and as scaffolds for the design of QS-based anti-infective therapeutics against S. pneumoniae infections.