Chimeric protein probes for C5a receptors through fusion of the anaphylatoxin C5a core region with a small-molecule antagonist

Chemical methods for studying the crosstalk between histone H2B ubiquitylation and H3 methylation

“…In addition to the photo‐sensitive auxiliary that was used to incorporate Ub at H2BK120 site, acidic‐sensitive auxiliary and δ‐mercaptolysine (mK)‐based approaches have also been used to prepare H2BK120ub with a native isopeptide bond (Figure 2B,C). 66,68–71 The total chemical synthesis of ubiquitylated histones has also been accomplished from basic amino acid building blocks using current methods 72–77 …”

“…66,[68][69][70][71] The total chemical synthesis of ubiquitylated histones has also been accomplished from basic amino acid building blocks using current methods. [72][73][74][75][76][77] The chemically synthesized H2BK120ub was incorporated into nucleosomes and used to investigate the effect of Ub on Dot1L methyltransferase activity. The level of methylation activity observed on ubiquitylated mono-nucleosomes was much higher than that observed on unmodified ones, establishing a direct biochemical connection between H2BK120ub and Dot1L-mediated H3K79me.…”

“…In 2016, a site-directed photo-crosslinking strategy wherein a H2BK120ub carrying a diazirine photo-crosslinker within the aforementioned functional hot-spot of Ub was developed to determine whether this Ub hot-spot engages Dot1L or the nucleosomal surface (Figure 5). 55 The Ub (64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76) hydrazide bearing a diazirine at Leu71 was synthesized by SPPS and then ligated with the requisite Ub thioester expressed using intein-based thiolysis. Then, the temporary Glu-to-Cys mutation for ligation at residue 64 was alkylated with bromoacetic acid to produce an analog of the native glutamate.…”

Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides†

“…Lactam cyclic peptides have attracted widespread attention recently due to their structural rigidity, metabolic stability, and interesting biological activity; [ 1‐7 ] and the Asp‐based lactam cyclic peptide drug bremelanotide (Scheme 1), a highly potent synthetic analogue of α‐melanocyte‐stimulating hormone, was recently approved by FDA. [ 8 ] Asp‐based lactam cyclic peptides are usually synthesized by Fmoc solid‐phase synthesis (SPPS), [ 9‐15 ] which generally entails removal of the temporary protecting groups on the side chains of Asp and Lys (or their derivatives) prior to on‐resin Asp‐Lys lactam cyclization.…”

Comparison of different strategies towards the chemical synthesis of long‐chain scorpion toxin AaH‐II

“…The structure of Na v 1.7‐Na v PaS channel in complex with the AaH‐II has been recently elucidated 15 . Given that mammalian Na v 1.7 is an important drug target for chronic pain, the method for the preparation of AaH‐II and its derivatives in high efficiency will be helpful to the in‐depth study of the structure and function of Na v 1.7, as well as related drug discovery 16,17 …”