A Pro-Fluorescent Ubiquitin-Based Probe to Monitor Cysteine-Based E3 Ligase Activity.

Protein post-translational modification with ubiquitin (Ub) is a versatile signal regulating almost all aspects of cell biology, and an increasing range of diseases is associated with impaired Ub modification. In this light, the Ub system offers an attractive, yet underexplored route to the development of novel targeted treatments. A promising strategy for small molecule intervention is posed by the final components of the enzymatic ubiquitination cascade, E3 ligases, as they determine the specificity of the protein ubiquitination pathway.

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

The 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.

Synthesis of N-Protected Amino Sulfenyl Methyl Formamides and Sulfonyl Methyl Formamides: A Simple Protocol.

Chiral amino acid-derived formamides represent one of the most versatile components in multicomponent reactions. Herein, we describe a facile synthesis of N-protected amino sulfenyl methyl formamides and sulfonyl methyl formamides the Mannich reaction of N-protected amino alkyl thiols followed by oxidation using 3-chloroperbenzoic acid (-CPBA). This protocol is applicable to a wide range of Fmoc- and Cbz-protected amino acids.

Tubulysin Synthesis Featuring Stereoselective Catalysis and Highly Convergent Multicomponent Assembly.

A concise and modular total synthesis of the highly potent N-desacetoxytubulysin H () has been accomplished in 18 steps in an overall yield of up to 30%. Our work highlights the complexity-augmenting and route-shortening power of diastereoselective multicomponent reaction (MCR) as well as the role of bulky ligands to perfectly control both the regioselective and diastereoselective synthesis of tubuphenylalanine in just two steps. The total synthesis not only provides an operationally simple and step economy but will also stimulate major advances in the development of new tubulysin analogues.

Synthesis of aryl-thioglycopeptides through chemoselective Pd-mediated conjugation.

We 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.