Rational design of NT-PSMA heterobivalent probes for prostate cancer theranostics.

Targeting the prostate-specific membrane antigen (PSMA) with radiopharmaceuticals for imaging and/or therapy has demonstrated significant advancement in the management of prostate cancer patients. However, PSMA targeting remains unsuccessful in prostate cancers with low expression of PSMA, which account for 15% of cases. The neurotensin receptor-1 (NTS) has been highlighted as a suitable oncotarget for imaging and therapy of PSMA-negative prostate cancer lesions.

Exogenous C-S Lyase Enzyme, a Potential Tool To Release Aromas in Wine or Beer?

Varietal thiols have an impact on the overall aroma of many white, rosé, and red wines and beers. They originate from the metabolism of non-odorant aroma precursors by yeast during the fermentation step, via an intrinsic enzyme, the carbon-sulfur β-lyase (CSL, EC 4.4.

Design, Synthesis, and Biological Evaluation of the First Radio-Metalated Neurotensin Analogue Targeting Neurotensin Receptor 2.

Neurotensin receptor 2 (NTS) is a well-known mediator of central opioid-independent analgesia. Seminal studies have highlighted NTS overexpression in a variety of tumors including prostate cancer, pancreas adenocarcinoma, and breast cancer. Herein, we describe the first radiometalated neurotensin analogue targeting NTS.

Fluorescent P-Hydroxyphosphole for Peptide Labeling through P-N Bond Formation.

Synthesis of fluorescent P-hydroxybinaphtylphosphole-oxide or -sulfide was achieved by trapping a binaphtyl dianion with methyl dichlorophosphite or P-(N,N-diethylamino)dichlorophosphine, followed by oxidation or sulfuration of the P-center. After saponification or acid hydrolysis, the P-hydroxyphospholes were coupled to peptides using the coupling agent BOP, under the conditions required for the synthesis in solution or on a solid support. This new method was illustrated by the labeling of the JMV2959, a potent antagonist of the Growth Hormone Secretagogue Receptor type 1a (GHS-R1a).

Metabolically stable neurotensin analogs exert potent and long-acting analgesia without hypothermia.

The endogenous tridecapeptide neurotensin (NT) has emerged as an important inhibitory modulator of pain transmission, exerting its analgesic action through the activation of the G protein-coupled receptors, NTS1 and NTS2. Whereas both NT receptors mediate the analgesic effects of NT, NTS1 activation also produces hypotension and hypothermia, which may represent obstacles for the development of new pain medications. In the present study, we implemented various chemical strategies to improve the metabolic stability of the biologically active fragment NT(8-13) and assessed their NTS1/NTS2 relative binding affinities.

Silicon-Containing Neurotensin Analogues as Radiopharmaceuticals for NTS-Positive Tumors Imaging.

Several independent studies have demonstrated the overexpression of NTS in various malignancies, which make this receptor of interest for imaging and therapy. To date, radiolabeled neurotensin analogues suffer from low plasmatic stability and thus insufficient availability for high uptake in tumors. We report the development of Ga-radiolabeled neurotensin analogues with improved radiopharmaceutical properties through the introduction of the silicon-containing amino acid trimethylsilylalanine (TMSAla).

Insightful Backbone Modifications Preventing Proteolytic Degradation of Neurotensin Analogs Improve NT-Induced Protective Hypothermia.

Therapeutic hypothermia represents a brain-protective strategy for multiple emergency situations, such as stroke or traumatic injury. Neurotensin (NT), which exerts its effects through activation of two G protein-coupled receptors, namely NTS1 and NTS2, induces a strong and long-lasting decrease in core body temperature after its central administration. Growing evidence demonstrates that NTS1 is the receptor subtype mediating the hypothermic action of NT.

Revisiting the evaluation strategy of varietal thiol biogenesis.

The varietal thiols 3-mercaptohexan-1-ol (3MH), 3-mercaptohexyl acetate (3MHA), and 4-mercapto-4-methylpentan-2-one (4MMP) are key aroma compounds in wine due to the tropical notes they impart. They are released by yeast during alcoholic fermentation from different precursors. However, a large part of 3MH origin remains unknown.

Phospholyl(borane) Amino Acids and Peptides: Stereoselective Synthesis and Fluorescent Properties with Large Stokes Shift.

The synthesis of phospholyl(borane) amino acids was stereoselectively achieved by reaction of phospholide anion with iodo α-amino ester derived from l-aspartic acid or l-serine, followed by in situ complexation with borane. Phospholyl(borane) amino acids are easy to store and can be subjected to direct transformation into the corresponding free phospholyl, gold complex, oxide or sulfur derivatives as well as phospholinium salts, thus offering a variety of side chains. After selective deprotection of carboxylic function or amine, C- or N- peptide coupling with an alanine moiety proved the possible incorporation into peptides.

First identification and quantification of S-3-(hexan-1-ol)-γ-glutamyl-cysteine in grape must as a potential thiol precursor, using UPLC-MS/MS analysis and stable isotope dilution assay.

Varietal thiols are key aroma compounds in wine issued from multiple and complex origins. Several precursor families have been identified in grapes and must and have been widely studied. But a large part of thiol origin still remains unknown.

Silicon-Containing Amino Acids: Synthetic Aspects, Conformational Studies, and Applications to Bioactive Peptides.

Unnatural α-amino acids form a family of essential molecules used for, among other applications, the synthesis of modified peptides, to improve resistance to proteolytic enzyme degradation, and to modulate physico- and biochemical properties of bioactive peptides as well as chiral inducers in asymmetric synthesis. Among them, silicon-containing unnatural amino acids are becoming an interesting new class of building blocks. The replacement of carbon atoms in bioactive substances with silicon is becoming increasingly popular.

Efficient synthesis of (P-chirogenic) o-boronated phosphines from sec-phosphine boranes.

An efficient synthesis of boronated phosphines with an o-phenylene-bridge prepared from sec-phosphine boranes and using benzyne chemistry is reported. Successive reactions of sec-phosphine boranes with n-BuLi and 1,2-dibromobenzene, and then with boron reagents, afford the o-boronatophenylphosphine derivatives in 71% yields. The use of P-chirogenic sec-phosphine boranes leads to the free boronated phosphines with retention of configuration at the P-center after decomplexation.

P-chirogenic organocatalysts: application to the aza-Morita-Baylis-Hillman (aza-MBH) reaction of ketimines.

The P-chirogenic organocatalysts were found to promote the enantioselective aza-Morita-Baylis-Hillman reaction of ketimines derived from acyclic α-keto esters. In the P-chirogenic organocatalyzed aza-MBH reactions, α,α-disubstituted α-amino acid derivatives were obtained in high yields with high enantioselectivities (up to 97% ee).

o-(Hydroxyalkyl)phenyl P-chirogenic phosphines as functional chiral Lewis bases.

The stereoselective synthesis of P-chirogenic phosphines bearing an o-hydroxyalkyl chelating arm is described. The synthesis is based either on the hydroxyalkylation of P-chirogenic o-bromophenylphosphines (borane) or on their carbonatation and then reduction. The hydroxyalkylation with benzaldehyde or pivalaldehyde affords a mixture of epimers which are isolated by chromatography and characterized by their X-ray structures.

Stereoselective synthesis of unsaturated and functionalized L-NHBoc amino acids, using Wittig reaction under mild phase-transfer conditions.

The stereoselective synthesis of a new amino acid phosphonium salt was described by quaternization of melting triphenylphosphine with the γ-iodo NHBoc-amino ester, derived from L-aspartic acid. The deprotection of the carboxylic acid function to afford the phosphonium salt with a free carboxylic acid group was achieved by a palladium-catalyzed desallylation reaction. This phosphonium salt was used in the Wittig reaction with aromatic or aliphatic aldehydes and trifluoroacetophenone, under solid-liquid phase-transfer conditions in chlorobenzene and in the presence of K(3)PO(4) as weak base, to afford the corresponding unsaturated amino acids without racemization.

Rhodium(I)-catalyzed borylation of nitriles through the cleavage of carbon-cyano bonds.

The reaction of aryl cyanides with diboron in the presence of a rhodium/Xantphos catalyst and DABCO affords arylboronic esters via carbon-cyano bond cleavage. This unprecedented mode of reactivity for a borylrhodium species allows the regioselective introduction of a boryl group in a late stage of synthesis.

Efficient synthesis of quaternary and P-stereogenic phosphonium triflates.

An efficient and general method for the preparation of achiral and chiral phosphonium salts is reported. This synthesis is based on the quaternization of phosphines and their derivatives with arynes generated in situ from 2-(trimethylsilyl)aryl triflates. This methodology is successfully applied to the synthesis of new valuable P-stereogenic phosphonium triflates.