An efficient synthesis of a 4'-phosphonodifluoromethyl-3'-formyl-phenylalanine containing SRC SH2 ligand.
A CuBr-mediated, regioselective cross-coupling between methyl 2,5-diiodobenzoate (4) and [(diethoxyphosphinyl)difluoromethyl]zinc bromide is reported. Palladium-catalyzed incorporation of an amino acid side chain, followed by subsequent modifications resulted in the rapid construction of 2. Compound 2 was designed to engage Cys188 of the Src SH2 domain, however, this was not observed spectroscopically.
The formation of a covalent complex between a dipeptide ligand and the src SH2 domain.
The X-ray crystal structure of the src SH2 domain revealed the presence of a thiol residue (Cys 188) located proximal to the phosphotyrosine portion of a dipeptide ligand. An aldehyde bearing ligand (1) was designed to position an electrophilic carbonyl group in the vicinity of the thiol. X-ray crystallographic and NMR examination of the complex formed between (1) and the src SH2 domain revealed a hemithioacetal formed by addition of the thiol to the aldehyde group with an additional stabilizing hydrogen bond between the acetal hydroxyl and a backbone carbonyl.
Rubik's for cryptographers
Hard mathematical problems are at the core of security arguments in cryptography. In this paper, we study mathematical generalizations of the famous Rubik’s cube puzzle, namely the factorization, representation and balance problems in non-Abelian groups. These problems arise naturally when describing the security of Cayley hash functions, a class of cryptographic hash functions with very interesting properties. The factorization problem is also strongly related to a famous long-standing conjecture of Babai, at the intersection of group theory and graph theory. A constructive proof of Babai’s conjecture would make all Cayley hash functions insecure, but on the other hand it would have many positive applications in graph theory and computer science. In this paper, we classify existing attacks against Cayley hash functions and we review known results on Babai’s conjecture. Despite recent cryptanalytic progress on particular instances, we show that the factorization, representation and balance problems presumably remain good sources of cryptographic hard problems. Our study demonstrates that Cayley hash functions deserve further interest by the cryptography community.