This paper introduces the unnatural amino acids m-Abc2K and o-Abc2K as nanometer-sized building blocks for the creation of water-soluble macrocycles with well-defined shapes. m-Abc2K and o-Abc2K are homologues of the nanometer-sized amino acid Abc2K, which we recently introduced for the synthesis of water-soluble molecular rods of precise length. [J. Am. Chem. Soc. 2007, 129, 7272]. Abc2K is linear (180°), m-Abc2K creates a 120° angle, and o-Abc2K creates a 60° angle. m-Abc2K and o-Abc2K are derivatives of 3’-amino-[1,1’-biphenyl]-4-carboxylic acid and 2’-amino-[1,1’-biphenyl]-4-carboxylic acid, with two propyloxyammonium side chains for water solubility.
Abstract
This paper introduces the unnatural amino acids m-Abc2K and o-Abc2K as nanometer-sized building blocks for the creation of water-soluble macrocycles with well-defined shapes. m-Abc2K and o-Abc2K are homologues of the nanometer-sized amino acid Abc2K, which we recently introduced for the synthesis of water-soluble molecular rods of precise length (J. Am. Chem. Soc. 2007, 129, 7272). Abc2K is linear (180°), m-Abc2K creates a 120° angle, and o-Abc2K creates a 60° angle. m-Abc2K and o-Abc2K are derivatives of 3′-amino-(1,1′-biphenyl)-4-carboxylic acid and 2′-amino-(1,1′-biphenyl)-4-carboxylic acid, with two propyloxyammonium side chains for water solubility. m-Abc2K and o-Abc2K are prepared as Fmoc-protected derivatives Fmoc-m-Abc2K(Boc)-OH (1a) and Fmoc-o-Abc2K(Boc)-OH (1b). These derivatives can be used alone or in conjunction with Fmoc-Abc2K(Boc)-OH (1c) as ordinary amino acids in Fmoc-based solid-phase peptide synthesis. Building blocks 1a−c were used to synthesize macrocyclic “triangles” 9a−c, “parallelograms” 10a,b, and hexagonal “rings” 11a−d. The macrocycles range from a trimer to a dodecamer, with ring sizes from 24 to 114 atoms, and are 1−4 nm in size. Molecular modeling studies suggest that all the macrocycles except 10b should have well-defined triangle, parallelogram, and ring shapes if all of the amide linkages are trans and the o-alkoxy substituents are intramolecularly hydrogen bonded to the amide NH groups. The macrocycles have good water solubility and are readily characterized by standard analytical techniques, such as RP-HPLC, ESI-MS, and NMR spectroscopy. 1H and 13C NMR studies suggest that the macrocycles adopt conformations with all trans-amide linkages in CD3OD, that the “triangles” and “parallelograms” maintain these conformations in D2O, and that the “rings” collapse to form conformations with cis-amide linkages in D2O.
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CPC Scientific Inc., a leading global peptide CRDMO (Contract Research, Development, and Manufacturing Organization) has invested in a new peptide API (Active Pharmaceutical Ingredient) manufacturing site, bringing many new jobs to Rocklin, California. The 41,000 sq ft facility located at 3880 Atherton Rd, Rocklin, CA 95765 will be utilized to manufacture clinical to commercial grade peptide products for increased manufacturing capacity and will diversify CPC Scientific’s supply chain.
CPC Scientific is entering an exciting period of growth and innovation for peptide and oligonucleotide therapeutic development and manufacturing, and we will continue to provide therapeutic APIs to pharmaceutical and biotech companies around the world. We are very pleased to partner with the City of Rocklin, California to bring manufacturing and Life-Science jobs to local American workers,” said Shawn Lee, PhD, CEO.
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- Research, Takeda Pharmaceutical Company Limited, 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan
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Mogford, Jon E., George E. Davis, Steven H. Platts, and Gerald A. Meininger. Circulation research 79, no. 4 (1996): 821-826.
Locmi-AKH-I, cycloAKH (cyclo[LNFTPNWG]
CPC Scientific is pleased to announce and welcome David A. Godkin as VP of Business Operations! David will be responsible for the growth and development of our HR department and facilities management division. He brings 20+ years of experience in human resources and facility operations from the peptide industry. We are confident David will have […]
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Peptides [TDN-qFAM, C-(PEG)2-K(CPQ2)-GGGSRPfGG-5FAM] were obtained from Tufts University Peptide Core Facility or CPC Scientific, Inc (USA)
