CCDC 1520333: Experimental Crystal Structure Determination

Related Article: Thimmalapura M. Vishwanatha, Katarzyna Kurpiewska, Justyna Kalinowska-Tłuścik, and Alexander Dömling|2017|J.Org.Chem.|82|9585|doi:10.1021/acs.joc.7b01615,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Design of GPR54 (Kiss1r) crosslinker peptides: new tools to study G protein-coupled receptors (GPCR) localization and function

International audienc

CCDC 1520047: Experimental Crystal Structure Determination

Related Article: Thimmalapura M. Vishwanatha, Katarzyna Kurpiewska, Justyna Kalinowska-Tłuścik, and Alexander Dömling|2017|J.Org.Chem.|82|9585|doi:10.1021/acs.joc.7b01615,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Synthesis of aryl-thioglycopeptides through chemoselective Pd-Mediated conjugation

International audienceWe describe herein a Pd-catalyzed methodology for the thioglycoconjugation of iodoaryl peptides and aminoacids. This operationally simple process occurs under semi-aqueous conditions and displays wide substrate scope. The strategy has been successfully applied to both the thioglycosylation of unprotected peptides and the generation of thioglyco-aminoacid building blocks, including those suitable for solid phase peptide synthesis. To demonstrate the broad potential of this technique for late stage functionalization, we successfully incorporated challenging unprotected β-S-GlcNAc- and α-S-GalNAc- derivatives into very long unprotected peptides. This study opens the way to new applications in chemical biology, considering the well-recognized advantages of S-glycosides over O-glycosides in terms of resistance towards both enzymatic and chemical degradation

A customized long acting formulation of the kisspeptin analog C6 triggers ovulation in anestrus ewe

International audienceThe modulation of the kisspeptin system holds promise as a treatment for human reproductive disorders and for managing livestock breeding. The design of analogs has overcome some unfavorable properties of the endogenous ligands. However, for applications requiring a prolongation of drug activity, such as ovulation induction in the ewe during the non-breeding season, additional improvement is required. To this aim, we designed and tested three formulations containing the kisspeptin analog C6. Two were based on polymeric nanoparticles (NP1 and NP2) and the third was based on hydrogels composed of a mixture of cyclodextrin polymers and dextran grafted with alkyl side chains (MD/pCD). Only the MD/pCD formulation prolonged C6 activity, as shown by monitoring luteinizing hormone (LH) plasma concentration (elevation duration 23.4 +/- 6.1, 13.7 +/- 4.7 and 12.0 +/- 2.4 h for MD/pCD, NP1 and NP2, respectively). When compared with the free C6 (15 nmol/ewe), the formulated (MD/pCD) doses of 10, 15 and 30 nmol/ewe, but not the 90 nmol/ewe dose, provided a more gradual release of C6 as shown by an attenuated LH release during the first 6 h post-treatment. When tested during the non-breeding season without progestogen priming, only, the formulated 30 nmol/ewe dose triggered ovulation (50% of ewes). Hence, we showed that a formulation with an adapted action time would improve the efficacy of C6 with respect to inducing ovulation during the non-breeding season. This result suggests that formulations containing a kisspeptin analog might find applications in the management of livestock reproduction but also point to the possibility of their use for the treatment of some human reproductive pathologies

Synthesis of aryl-Thioglycopeptides through chemoselective Pd-catalyzed conjugation

International audienc

Treating mares with the long-acting kisspeptin analog C6 increases circulating gonadotropins but does not trigger ovulation

International audienceThe role of the neuropeptide kisspeptin (Kp) in mammalian reproduction is well established. Nevertheless, species-specific differences exist. In the horse, administration of the shortest endogenous Kp isoform, Kp10, is unable to trigger ovulation even though it increases plasma gonadotropins concentrations. To check if this issue would be dependent on Kp10 short half-life, we tested two degradation-resistant Kp analogs. The first analog was based on the equine Kp10 sequence (eC6), the second on the ovine Kp10 sequence (oC6). During the non-breeding season, a dose of 150 nmol/mare of either molecule had no significant effect on LH concentration, while oC6 provided a better stimulation of FSH than eC6 (p = 0.01). Furthermore, oC6 was more effective when injected intravenously than intramuscularly. Due to its best pharmacodynamics profile, oC6 (150 nmol/mare) was probed for ovulation induction during the breeding season. The molecule was injected during the preovulatory phase when the follicle diameter ranged from 34 to 37 mm and a uterine oedema was observed. oC6 consistently increased the total amount of gonadotropins released (FSH, p = 0.01 and LH, p = 0.02). However, as shown by transrectal ultrasonography and plasma progesterone levels, oC6 did not anticipate ovulation compared to the control group. Our results provide further evidence of the peculiar reproductive endocrinology of the mare but leave open questions regarding the exact role of Kp in the control of ovulation and breeding in the mare, which we attempt to identify and discuss