133849-27-1Relevant articles and documents
Repurposing the 3-Isocyanobutanoic Acid Adenylation Enzyme SfaB for Versatile Amidation and Thioesterification
Zhu, Mengyi,Wang, Lijuan,He, Jing
supporting information, p. 2030 - 2035 (2020/11/30)
Genome mining of microbial natural products enables chemists not only to discover the bioactive molecules with novel skeletons, but also to identify the enzymes that catalyze diverse chemical reactions. Exploring the substrate promiscuity and catalytic mechanism of those biosynthetic enzymes facilitates the development of potential biocatalysts. SfaB is an acyl adenylate-forming enzyme that adenylates a unique building block, 3-isocyanobutanoic acid, in the biosynthetic pathway of the diisonitrile natural product SF2768 produced by Streptomyces thioluteus, and this AMP-ligase was demonstrated to accept a broad range of short-chain fatty acids (SCFAs). Herein, we repurpose SfaB to catalyze amidation or thioesterification between those SCFAs and various amine or thiol nucleophiles, thereby providing an alternative enzymatic approach to prepare the corresponding amides and thioesters in vitro.
N-Carboxyanhydride-Mediated Fatty Acylation of Amino Acids and Peptides for Functionalization of Protocell Membranes
Izgu, Enver Cagri,Bj?rkbom, Anders,Kamat, Neha P.,Lelyveld, Victor S.,Zhang, Weicheng,Jia, Tony Z.,Szostak, Jack W.
supporting information, p. 16669 - 16676 (2017/01/10)
Early protocells are likely to have arisen from the self-assembly of RNA, peptide, and lipid molecules that were generated and concentrated within geologically favorable environments on the early Earth. The reactivity of these components in a prebiotic environment that supplied sources of chemical energy could have produced additional species with properties favorable to the emergence of protocells. The geochemically plausible activation of amino acids by carbonyl sulfide has been shown to generate short peptides via the formation of cyclic amino acid N-carboxyanhydrides (NCAs). Here, we show that the polymerization of valine-NCA in the presence of fatty acids yields acylated amino acids and peptides via a mixed anhydride intermediate. Notably, Nα-oleoylarginine, a product of the reaction between arginine and oleic acid in the presence of valine-NCA, partitions spontaneously into vesicle membranes and mediates the association of RNA with the vesicles. Our results suggest a potential mechanism by which activated amino acids could diversify the chemical functionality of fatty acid membranes and colocalize RNA with vesicles during the formation of early protocells.
A modular approach towards drug delivery vehicles using oxanorbornane-based non-ionic amphiphiles
Janni, D. Sirisha,Reddy, U. Chandrasekhar,Saroj, Soumya,Muraleedharan
, p. 8025 - 8032 (2016/12/18)
The self-assembly of non-ionic amphiphiles with a hydroxylated oxanorbornane head-group was controlled using amino acid units as spacers between hydrophilic and lipophilic domains to get spherical supramolecular aggregates. The ability of these systems to harbour therapeutic agents like ibuprofen, and their drug-release profiles were evaluated. Apart from directing the assembly, the intervening amino acid unit was found to help in drug entrapment as well. The presence of cholesterol improved their drug-loading ability, and an encapsulation efficiency of up to 66% was shown by the formulation containing the phenylalanine residue as the spacer (NC1c). There was no burst release, and 45% drug release was observed at the end of 24 h in this case (cf. soyaphosphatidylcholine based formulation = 49%). The results from SEM, Cryo-TEM, PXRD and confocal microscopic studies with some insights into molecular packing in this class of aggregates are also included.
A systematic understanding of gelation self-assembly: solvophobically assisted supramolecular gelation via conformational reorientation across amide functionality on a hydrophobically modulated dipeptide based ambidextrous gelator, N-n-acyl-(l)Val-X(OBn), (X = 1,ω-amino acid)
Haldar, Saubhik,Karmakar, Koninika
, p. 66339 - 66354 (2015/08/18)
A systematic investigation on gelation self-assembly has been performed on a hydrophobically modulated dipeptide based ambidextrous gelator, N-n-acyl-(l)Val-X(OBn), (X = 1,ω-amino acid). To elucidate the effect of hydrophobic tuning on gelator architecture towards its gelation self-assembly, three sets of gelators with a common formula: CmH2m+1C(=O)NH(l)Val(C=O)NH-(CH2)n-(C=O)OBn, were synthesized, Set-I includes gelators with n = 2, m = 9, 11, 13, 15, 17, for Set-II it is n = 2, 3, 5, m = 13 and Set-III comprises of two isomeric gelators (n = 2, m = 15; n = 10, m = 7). Gelation has been critically analyzed in various apolar (aromatic and aliphatic) and polar (protic and aprotic) solvents using FESEM, CD, IR, WAXRD and rheological studies. Obtained results reveal that π-π type interaction dictates the primary molecular alignment and positioning of amide functionality across the aliphatic chain which influences the peptidic orientation in parallel (when m > n) or antiparallel (when m gel and yield stress of gel systems increases with m, but for a given m, the trend goes apparently inverse with the increasing n. Circular dichroism (CD) studies suggest an intriguing evidence of non-planarity of amide plane during self-assembly, highlighting the involvement of conformational change taking place during molecular organization towards its gelation. Despite complex nature of solvent-gelator interaction, the effect of H-bonding component of solubility parameters was found to have a significant role on self-assembly. Overall, supramolecular forces acting at specific functionalities encrypted in gelator backbone must overcome the solvation energy with synergic assistance of solvophobic effect towards stabilization of gel-network with optimum gelator backbone conformation for achieving required enthalpic contribution for self-assembly.
