IBMM has recently acquired this wonderful UPLC and mass-spectrometry toy! It is an Aquity Hclass UPLC (Pierre Sanchez to the left, the engeneer that operates it) produced by Waterstm that can sustain the amazing 15000 psi! While other HPLC would crumble under such pressure this fine equipment provides an amazing HPLC separation! Getting to 95% purity just got harder in our team!
The European Medicines Agency (EMA) has granted marketing authorization for MacrilenTM (JMV 1843), an orally available ghrelin agonist developed in our team ! Macrilen is used for diagnosis of adult growth hormone deficiency (AGHD). The approval came following the Committee for Medicinal Products for Human Use (CHMP) positive opinion of MacrilenTM.
People who have AGHD can include those who were GH deficient as children and become adults with AGHD, or adults who become GH deficient. In adults, GH deficiency could develop when your pituitary gland or hypothalamus is damaged due to tumors, surgery, radiation, or traumatic brain injury. GH is important for adults to support healthy tissue and organs. GH is released in pulses, so measuring your blood for too little GH (also known as a deficiency) may be hard. MacrilenTM, orally administered, will stimulate GH secretion in the circulation, which level can then be evaluated by simple blood samples.
Alice Legru, Kévin Bourbiaux, Christophe Cantelli and Yohan Malki attended the 26th Young Research Fellows Meeting which took place on 20th – 22nd February at the Faculty of Pharmacy of Paris. Alice did a great 15 minutes oral communication while and Kévin, Christophe and Yohan presented posters.
Titouan is the laureate of the “Prix Initiative Jeune” of Fondation Banque Populaire du Sud. He received a grant to participate to the “Sol-Gel Conference” congress in St. Petersburg in August. This congress will be an opportunity to present his thesis work.
Happy, healthy and prosperous 2019 to all the members and friends of IBMM peptide team !
1,4-Disubstituted-1,2,3-triazole (Tz) is widely used in peptides as a trans-amide bond mimic, despite having hazardous effects on the native peptide activity. The impact of amide bond substitution by Tz on peptide secondary structures is scarcely documented. We performed a Tz scan, by systematically replacing peptide bonds following the Aib residues with Tz on two model peptaibols: alamethicin F50/5 and bergofungin D, which adopt stable α- and 310 helices, respectively. We observed that the Tz insertion, whatever its position in the peptide sequences, abolished their antimicrobial activity. The structural consequences of this insertion were further investigated using CD, NMR and X-ray diffraction. Importantly, five crystal structures that were incorporated with Tz were solved, showing various degrees of alteration of the helical structures, from minor structural perturbation of the helix to partial disorder. Together, these results showed that Tz insertions impair helical secondary structures.
Chemistry. 2018 Dec 12. doi: 10.1002/chem.201804404. Epub 2018 Nov 15
Simon M, Milbeo P, Liu H, André C, Wenger E, Martinez J, Amblard M, Aubert E, Legrand B, Calmès M.
12/10-Helices constitute suitable templates that can be used to design original structures. Nevertheless, they often suffer from a weak stability in polar solvents because they exhibit a mixed hydrogen-bond network resulting in a small macrodipole. In this work, stable and functionalizable 12/10-helices were developed by alternating a highly constrained β2, 3, 3 -trisubstituted bicyclic amino acid (S)-1-aminobicyclo[2.2.2]octane-2-carboxylic acid ((S)-ABOC) and an acyclic substituted β-homologated proteinogenic amino acid (l-β3 -hAA). Based on NMR spectroscopic analysis, it was shown that such mixed β-peptides display well-defined right-handed 12/10-helices in polar, apolar, and chaotropic solvents; that are, CD3 OH, CDCl3 , and [D6 ]DMSO, respectively. The stability of the hydrogen bonds forming the C10 and C12 pseudocycles as well as the benefit provided by the use of the constrained bicyclic ABOC versus typical acyclic β-amino acids sequences when designing 12/10-helix were investigated using NH/ND NMR exchange experiments and DFT calculations in various solvents. These studies showed that the β3 -hAA/(S)-ABOC helix displayed a more stable hydrogen-bond network through specific stabilization of the C10 pseudocycles involving the bridgehead NH of the ABOC bicyclic scaffold.
The paper of Nicolas is just accepted in Eur. J. Org. Chem.
He took advantage of Surface Enhanced Raman Spectroscopy to design peptide-adenine conjugates as candidates for their use as serine protease substrates.
Thanks to a Merlion grant, Gilles and Laurine spent 2 weeks in Singapore, in Pr. Sing Yian Chew’s lab at the School of Chemical and Biomedical Engineering, Nanyang Technological University. This trip was an opportunity to implant sol-gel based hydrogel scaffolds (with a collagen-like peptide) into rats to assess their ability to repair spinal cord injury.
Gilles was an invited speaker at Korean Peptide Meeting in Yoesu, Korea.
He presented an overview of the work on peptide hydrogels and 3D printing