Practical Chemical Synthesis of Atypical Ubiquitin Chains by Using an Isopeptide-Linked Ub Isomer.

Chemical ubiquitination is an effective approach for accessing structurally defined, atypical ubiquitin (Ub) chains that are difficult to prepare by other techniques. Herein, we describe a strategy that uses a readily accessible premade isopeptide-linked 76-mer (isoUb), which has an N-terminal Cys and a C-terminal hydrazide, as the key building block to assemble atypical Ub chains in a modular fashion. This method avoids the use of auxiliary-modified Lys and instead employs the canonical and therefore more robust Cys-based native chemical ligation technique.

Efficient synthesis of longer Aβ peptides via removable backbone modification.

Longer amyloid-beta (Aβ) peptides (43 to 49 amino acids) play essential roles in the pathology of Alzheimer's disease (AD). The difficulty in the preparation of longer Aβ peptides is still an obstacle to elucidate their roles in AD. Herein we report a robust and efficient strategy for the chemical synthesis of longer Aβ peptides (Aβ48 and Aβ49).

Total chemical synthesis of photoactivatable proteins for light-controlled manipulation of antigen-antibody interactions.

We report the chemical synthesis of the first photo-activatable protein antigen that can be used to study antigen-antibody interaction mediated responses in B cells. This strategy facilitated fine tuning of the caged protein antigen to optimize its bioactivity and photochemical properties. One optimal molecule, HEL-KNPE, was totally inert to hen egg lysozyme (HEL)-specific B cells and could only restore its antigenicity upon photoactivation.

An efficient one-pot four-segment condensation method for protein chemical synthesis.

Successive peptide ligation using a one-pot method can improve the efficiency of protein chemical synthesis. Although one-pot three-segment ligation has enjoyed widespread application, a robust method for one-pot four-segment ligation had to date remained undeveloped. Herein we report a new one-pot multisegment peptide ligation method that can be used to condense up to four segments with operational simplicity and high efficiency.