Dye‐Labeled C^α‐Tetrasubstituted α‐Amino Acids

Abstract

We report the synthesis of pyrene-and carboxyfluorescein labeled C a -tetrasubstituted amino acids (TAAs). The fluorescent dye can be coupled to the TAA before or after its incorporation into a peptide sequence using a Suzuki-type CÀC bond formation.Introduction. -The biological activity of peptides and proteins is based on their conformation, which is related to the secondary structures of the amino acid sequence [1 -3]. In this context, the major drawback of small natural peptides is the conformational flexibility as well as the biological and chemical instability, which may hamper the investigation of biological processes or to perform structural studies. Therefore, the rational design and synthesis of peptides and peptidomimetics [4] [5] with defined structural properties [6] [7] attracted interest of chemists and biologists in the recent past. To stabilize or mimic the conformation of peptides, many different approaches were followed [8]. One very successful strategy is the disubstitution in aposition of amino acids [9], resulting in a conformational constrain and enabling this class of C

Recent advances in the synthesis and application of fluorescent α-amino acids

“…The most common coupling reaction used for the synthesis of fluorescent polyaromatic α-amino acids is the Suzuki-Miyaura reaction of α-amino acids bearing vinyl or aryl halide side-chains with polyaromatic boronic acids. [59][60][61][62][63] This has resulted in the preparation of a range of novel pyrene or terphenyl derived α-amino acids that have been incorporated into proteins and used as fluorescent tags or in FRET experiments. 61,63 For example, Hecht and co-workers used a Suzuki-Miyaura reaction of iodinated phenylalanine derivatives with biphenylboronic acids to give regioisomeric terphenyl analogues such as 29 (Scheme 17).…”