Spacer strategy

A second strategy is to attach a linker (also referred to as a handle or anchor) to the resin followed by assembly of the molecule. A linker is bifunctional spacer that serves to link the initial synthetic unit to the support in two discrete steps (Fig. 3). To attach a linker to a chloromethyl-PS resin, a phenol functionality such as handle 4 is used to form an ether bond (Fig. 4). To attach the same handle to an amino-functionalized support, acetoxy function 5 or a longer methylene spacer of the corresponding phenol is applied to form an amide bond. Both of these resins perform similarly and only differ in their initial starting resin [4], An alternative approach is to prepare a preformed handle in which the first building block is prederivatized to the linker and this moiety is attached to the resin. For peptide synthesis, this practice is common for the preparation of C-terminal peptide acids in order to reduce the amount of racemization of the a-carbon at the anchoring position [5],... 

The advantage of iterative strategies is based on the specific preparation of well defined structures and structurally perfect spacers of nanometer scale. This stepwise approach yields monodisperse material in contrast to other statistical routes. The use of the same reactants and the conversion of the same functional groups facilitates the synthetic effort compared with non-iterative methods. 

A few years later, the same group extended this strategy in order to access metabolically stable C-glycosyl clusters containing long-arm spacers via a sequence of transition metal-catalyzed transformations (Scheme 11).93 In this context, crossmetathesis reactions of various C-glycosyl compounds with alkenes having available... 

Two strategies for preparation of neutral and monocationic porphyrin models were used. The presence of a spacer arm directly attached to the meso phenyl position of the porphyrins gave access to a series of dimers with different substituents on the meso position and with different geometries. 

Using the same versatile modular synthetic strategy, the same group developed biotinylated bi- (438) and tetra-antennary (439) mannosylated glycoconjugates to capture and detect E. coli cells, and compared the relative capturing ability of these molecules to commercial polyclonal antibodies (Fig. 47).318 Instead of aliphatic spacers, tetraethylene glycol linkers were used to diminish nonspecific binding and to impart flexibility for a better fit in the active sites. 

The direct attachment of adequately substituted mexo-arylporphyrin to the saccharide units has been another synthetic strategy. Mexo-tetraaryl-porphyrins were used as templates to append, directly or by a spacer, several sugar units at the ortho, meta or para positions of the phenyl ring (Fig. 1). 

In this synthetic strategy, the macrocyclic antibiotic is covalently bonded to the silica matrix in two steps (1) chemical modification of the selector via reaction between suitable groups of the antibiotic and proper groups of the spacer, reacting also as a di- or trialkoxysilane (2) immobilization of the functionalized selector on unmodified silica particles. 

The spacer arm length between the hapten and the carrier is in the range of 6 to 8 A, which should eliminate any steric interference with carrier side chains. According to the protocol described by Schultz the haptens were coupled to BSA and KLH via A-(3-dimethylaminopropyl)-A -ethylcarbodiimide or the N-hydroxysuccinimide ester at pH 5.5 in water. Other coupling strategies include substitution with diazonium salts and reductive amination. The ratio of hapten-carrier range between 8 and 15 haptens per carrier. 

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