Solid-Phase O-Glycosylation with a Glucosamine Derivative for the Synthesis of a Glycopeptide

2017 ◽  
Vol 70 (10) ◽  
pp. 1151 ◽  
Author(s):  
Philip Ryan ◽  
Andy Hsien Wei Koh ◽  
Anna Elizabeth Lohning ◽  
Santosh Rudrawar
Keyword(s):  
Amino Acid ◽  
Building Block ◽  
Solid Phase ◽  
Hydroxyl Group ◽  
Side Chain ◽  
Efficient Synthesis ◽  
Direct Solid

An efficient synthesis of the O-linked glycosylamino acid Fmoc–l-Ser((Ac)3–β-d-GlcNAc)-OH building block is described. The utility of the method was demonstrated with direct solid-phase O-glycosylation of the hydroxyl group on the amino acid (Ser) side chain of a human α-A crystallin-derived peptide (AIPVSREEK) in nearly quantitative glycosylation yield.

Comparison of the Potency of 8-L-Arginine, 8-D-Arginine and 8-D-Homoarginine Vasopressin Analogs with Substituted Phenylalanine in Position 2

1994 ◽  
Vol 59 (6) ◽  
pp. 1439-1450 ◽  
Author(s):  
Miroslava Žertová ◽  
Jiřina Slaninová ◽  
Zdenko Procházka
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Basic Amino Acid ◽  
The Other ◽  
Side Chain ◽  
Inhibitory Potency ◽  
Phase Synthesis ◽  
Other Hand ◽  
Order Of Magnitude

An analysis of the uterotonic potencies of all analogs having substituted L- or D-tyrosine or -phenylalanine in position 2 and L-arginine, D-arginine or D-homoarginine in position 8 was made. The series of analogs already published was completed by the solid phase synthesis of ten new analogs having L- or D-Phe, L- or D-Phe(2-Et), L- or D-Phe(2,4,6-triMe) or D-Tyr(Me) in position 2 and either L- or D-arginine in position 8. All newly synthesized analogs were found to be uterotonic inhibitors. Deamination increases both the agonistic and antagonistic potency. In the case of phenylalanine analogs the change of configuration from L to D in position 2 enhances the uterotonic inhibition for more than 1 order of magnitude. The L to D change in position 8 enhances the inhibitory potency negligibly. Prolongation of the side chain of the D-basic amino acid in position 8 seems to decrease slightly the inhibitory potency if there is L-substituted amino acid in position 2. On the other hand there is a tendency to the increase of the inhibitory potency if there is D-substituted amino acid in position 2.

scholarly journals Regiodivergent Biocatalytic Hydroxylation of L-Glutamine Facilitated by Characterization of Non-Heme Dioxygenases from Non-Ribosomal Peptide Biosyntheses

2021 ◽  
Author(s):  
Hans Renata ◽  
Emily Shimizu ◽  
Christian Zwick
Keyword(s):  
Amino Acid ◽  
Building Block ◽  
Solid Phase ◽  
Functional Characterization ◽  
Free Standing ◽  
Substrate Specificities ◽  
Total Turnover

We report the functional characterization of two iron- and a-ketoglutarate-dependent dioxygenases that are capable of hydroxylating free-standing glutamine at its C3 and C4 position respectively. In particular, the C4 hydroxylase, Q4Ox, catalyzes the reaction with approximately 4,300 total turnover numbers, facilitating synthesis of a solid-phase compatible building block and stereochemical elucidation at the C4 position of the hydroxylated product. This work will enable the development of novel synthetic strategies to prepare useful glutamine derivatives and stimulate further discoveries of new amino acid hydroxylases with distinct substrate specificities.<br>

scholarly journals Regiodivergent Biocatalytic Hydroxylation of L-Glutamine Facilitated by Characterization of Non-Heme Dioxygenases from Non-Ribosomal Peptide Biosyntheses

2021 ◽  
Author(s):  
Hans Renata ◽  
Emily Shimizu ◽  
Christian Zwick
Keyword(s):  
Amino Acid ◽  
Building Block ◽  
Solid Phase ◽  
Functional Characterization ◽  
Free Standing ◽  
Substrate Specificities ◽  
Total Turnover

We report the functional characterization of two iron- and a-ketoglutarate-dependent dioxygenases that are capable of hydroxylating free-standing glutamine at its C3 and C4 position respectively. In particular, the C4 hydroxylase, Q4Ox, catalyzes the reaction with approximately 4,300 total turnover numbers, facilitating synthesis of a solid-phase compatible building block and stereochemical elucidation at the C4 position of the hydroxylated product. This work will enable the development of novel synthetic strategies to prepare useful glutamine derivatives and stimulate further discoveries of new amino acid hydroxylases with distinct substrate specificities.<br>

Interaction between the pili of Pseudomonas aeruginosa PAK and its carbohydrate receptor β-D-GalNAc(1->4) β-D-Gal analogs

1998 ◽  
Vol 44 (3) ◽  
pp. 307-311 ◽  
Author(s):  
Frank Schweizer ◽  
Hailong Jiao ◽  
Ole Hindsgaul ◽  
Wah Y Wong ◽  
Randall T Irvin
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Inhibitory Concentration ◽  
Binding Assay ◽  
Solid Phase ◽  
Hydroxyl Group ◽  
Side Chain ◽  
Surface Receptors ◽  
Order Of Magnitude ◽  
Epithelial Cell Surface ◽  
Solid Phase Binding

Pseudomonas aeruginosa employs pili to mediate adherence to epithelial cell surface receptors. Previously, it has been shown that the pilus adhesin of P. aeruginosa PAK binds to the ganglioside asialo-GM1. In particular, it was found that the carbohydrate sequence β-D-GalNAc(1->4) β-D-Gal is the minimal carbohydrate receptor sequence of asialo-GM1. To study the binding specificity of P. aeruginosa, O-modified and N-modified sugar analogs, where each hydroxyl group was substituted either by O-methyl or O-propyl and the acetamido group was changed to a propionamido group, were synthesized. The sugar analogs were evaluated as inhibitors in a competitive solid phase binding assay. The results demonstrate that the pili of P. aeruginosa PAK accepts a variety of sugar analogs possessing the sequence β-D-GalNAc(1->4) β-D-Gal. Most sugar analogs bind with a similar order of magnitude (50% inhibitory concentration (IC50) = 60-130 μM) except for the 2-O-propyl derivative 7 (IC50 = 8 ± 4 μM) compared with an IC50 of 79 ± 18 μM for the native compound. The significant increase in binding affinity of 2-O-propyl derivative 7 suggests that improved inhibitors of adhesion may be prepared by introducing a hydrophobic side chain at the 2-position of galactose.Key words: Pseudomonas aeruginosa, pili, adhesion, carbohydrate.

Efficient synthesis of a side-chain extended diaminodiacid for solid-phase synthesis of peptide disulfide bond mimics

2019 ◽  
Vol 60 (17) ◽  
pp. 1197-1201 ◽  
Author(s):  
Shuai-Shuai Sun ◽  
Junyou Chen ◽  
Rui Zhao ◽  
Donald Bierer ◽  
Jun Wang ◽  
...  
Keyword(s):  
Disulfide Bond ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Side Chain ◽  
Efficient Synthesis ◽  
Phase Synthesis

Phosphopeptide synthesis

1999 ◽  
Author(s):  
Peter D. White
Keyword(s):  
Building Block ◽  
Solid Phase ◽  
Benzyl Ester ◽  
Side Chain ◽  
Hydroxyl Groups ◽  
Principal Mechanism ◽  
Cellular Processes ◽  
Phosphoamino Acids ◽  
Silyl Groups ◽  
Block Approach

Protein phosphorylation mediated by protein kinases is the principal mechanism by which eukaryotic cellular processes are modulated by external physiological stimuli. Phosphopeptides are essential tools for the study of this process, serving as model substrates for phosphatases, as antigens for the production of antibodies against phosphorylated proteins, and as reference compounds for determining their physical parameters. The development of methods for the production of phosphopeptides has consequently attracted considerable interest over the last few years, and these endeavours have yielded reliable procedures which have now made their synthesis routine. There are two strategies used currently for the preparation of phosphopeptides: the building block approach, in which pre-formed protected phosphoamino acids are incorporated during the course of chain assembly, and the global phosphorylation method, which involves post-synthetic phosphorylation of serine, threonine, or tyrosine side-chain hydroxyl groups on the solid support. The building block procedure is certainly the more straightforward of the two approaches and has now become, owing to the availability of suitably protected phosphoamino acids, the standard method for the routine production of phosphopeptides. For the side-chain protection of phosphotyrosine in Fmoc/tBu-based solid phase synthesis, methyl, benzyl, t-butyl, dialkylamino, and silyl groups have been employed. Of these, benzyl is most useful as it is the most convenient to introduce and is rapidly removed during the TFA-mediated acidolysis step. Only the mono-benzyl ester, Fmoc-Tyr(PO(OBzl)-OH)-OH 1, is available commercially; the dibenzyl ester offers no practical benefit as it undergoes mono-debenzylation in the course of the piperidine-mediated Fmoc deprotection reaction. Also available commercially is Fmoc-Tyr(PO3H2)-OH 2. This derivative, despite having no phosphate protection, appears to work well, particularly in the synthesis of small- to medium-sized phosphopeptides; although formation of the pyrophosphate 3 can be a problem in peptides containing adjacent Tyr(PO3H2) residues. Phosphate triesters of serine and threonine are not compatible with Fmoc/tBu chemistry as they undergo β-elimination when treated with piperidine, resulting in the formation of dehydroalanine and dehydoaminobutyric acid, respectively For this reason, it was long believed that the building block approach could not be used for preparation of peptides containing these amino acids.

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