Building block approach

There are two strategies used currently for the preparation of phosphopeptides the building block approach, in which pre-formed protected phospho-amino 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 procedme 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/rBu-based solid phase synthesis, methyl (2), benzyl (3,4), r-butyl (5,6), dialkylamino (7), and silyl (8) 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 (9, 10), is available commercially the dibenzyl ester offers no 

Also available commercially is Fmoc-Tyr(P03H2)-OH 2 (12). 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(P03H2) residues (13,14). 

Sterols are a class of lipids containing a common steroid core of a fused four-ring structure with a hydrocarbon side chain and an alcohol group. Cholesterol is the primary sterol lipid in mammals and is an important constituent of cellular membranes. Oxidization and/or metabolism of cholesterol yield numerous oxysterols, steroids, bile acids, etc., many of which are important signaling molecules in biological systems. Cholesteryl esters esterified with a variety of fatty acyls are enriched in 

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R Unger, D Harel, S Wherland, JL Sussman. A 3-D building blocks approach to analyzing and predicting structure of proteins. Pi otems 5 355-373, 1989. 

A Generalized Design Approach to Power Supplies Introducing the Building-block Approach to Power Supply Design... 

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I 74 The Building-block Approach to Understanding Main-group-metal Complex Structures... 

While parallel synthesis of arrays of glycopeptides is readily achieved by implementation of the building-block approach (Scheme 14.1, Strategy 2),101 glycopeptide library synthesis in a combinatorial manner via the split-mix method has yet to prove routine. The difficulty lies in the structural analysis of the vast number of compounds generated in picomolar quantities on a single bead. Whereas peptides on... 

Scheme 14.1 Strategies for glycopeptide library synthesis Strategy 1 chemical or enzymatic glycosylation of peptide or glycopeptide Strategy 2 the building-block approach. While enzymes have not yet been used in the solid-phase synthesis of glycopeptide libraries, several resin-bound glycopeptides have been glycosylated enzymatically.36,114...

In general, the various synthesis strategies for nanocarbon hybrids can be categorized as ex situ and in situ techniques [3]. The ex situ ( building block ) approach involves the separate synthesis of the two components prior to their hybridization. One can rely on a plethora of scientific work to ensure good control of the component s dimensions (i.e. size, number of layers), morphology (i.e. spherical nanoparticles, nanowires) and functionalization. The components are then hybridized through covalent, noncovalent or electrostatic interactions. In contrast, the in situ approach is a one-step process that involves the synthesis of one of the components in the pres-... 

In this building-block approach, the components are synthesized separately and then hybridized via linking agents/methods that utilize covalent, noncovalent (van der Waals, n-n interactions, hydrogen bonding), or electrostatic interactions. The attachment of these building blocks often requires the chemical modification of at least one component to overcome the differences in surface chemistry. As a consequence deposition is often limited to the first layer. Excess nanoparticles can be removed by filtration or centrifugation. 

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