Sequential solid phase peptide synthesis

A sequential solid-phase peptide synthesis has been developed which makes use of both a photolabile linker and a photolabile protecting group (Scheme 8). The system is based on a tert-butyl ketone-derived linker, which is sensitive to... 

Redox-sensitive resin 24 designed for solid-phase peptide synthesis (SPPS) [29] was prepared from commercially available 2,5-dimethylben-zoquinone in seven steps [30] and loaded to a support via a Wittig reaction. Release of the peptide occurs using two sequential mild conditions, reduction with NaBH4 followed by TBAF-catalyzed cyclic ether formation (Scheme 8) which provide orthogonality to acid sensitive reactions. 

Zheng A, Shan D, Shi X, Wang B. A model resin linker for solid-phase peptide synthesis which can be cleaved using two sequential mild reactions. J Org Chem 1999 64 7459-7466. 

Finally, dendrimers have been synthesized using solid phase peptide synthesis resins, wherein the core is linked to the resin and the half-dendrimer (dendron) is built out from it in sequential steps (Marsh et al., 1996 Swali et al., 1997 Wells et al., 1998). The advantage of this method... 

This new approach involved alkylation of methyl 4-hydroxybenzoate with (354) using caesium bicarbonate as the acid scavenger [174]. The resulting amide ester (356) was sequentially deprotected and saponified to produce (357). Incorporation of the glutamic acid moiety was best accomplished using solid-phase peptide synthesis techniques and gave consistently better overall yields of (358) [102, 177]. 

Solid-phase peptide synthesis is based on the sequential addition of protected amino acids onto an insoluble support. Addition proceeds from carboxy terminus to amino terminus. The first amino acid is attached to a solid support by a linker and, if necessary, side-chain amino acid function is protected throughout chain assembly. The carboxy group of the in-coming, acylating amino acid is activated for coupling while its amino group is protected temporarily for each coupling step and then deprotected for the next cycle. The... 

Once the first amino acid is bound to the polymer, additional amino acids can be added sequentially. The steps of the solid phase peptide synthesis technique are illustrated in the accompanying scheme. In the last step, HF cleaves the polypeptide chain from the polymer. 

Aurilide (37) is a 26-membered cyclic depsipeptide (see Chapter 11, Subsection 11.5.6) that includes 3 A-methyl amino acids, isoleucic acid, and an aliphatic acid (Scheme 10.14). To elucidate structure-activity relationships, solid-phase peptide synthesis and solution-phase macrolactamiza-tion were planned. The linear precursor 38 was selected based on Yamada s previously reported approach. " The linear cyclization precursor 38 can be synthesized from solid-supported tetrapeptide 39 in two ways. In method A, isoleucic acid 40, aliphatic acid 41, and A-methylalanine 42 are coupled sequentially. An efficient coupling method for ester formation on polymer support is required. In method B, fragment 43 is prepared in advance to avoid ester formation on polymer... 

Some overlap between categories can occur. For example, the sequential synthesis of a polypeptide on a polymer support is equivalent to grafting the polypeptide onto the original polymer support, whereas each step of the solid-phase peptide synthesis can be regarded as a polymer-analogous transformation. 

The solid-phase synthesis of oligonucleotides consists basically of the sequential repetition of reaction steps similar to those previously described, with the properly protected monomeric nucleotides (for reviews, see Kossel and Seliger, 1975 Amarnath and Broom, 1977). The essential steps are like those used in solid-phase peptide synthesis. 

Combinatorial chemistry evolved from the field of solid state peptide synthesis in which peptides are prepared on a polymeric solid phase support. Such supports are traditionally composed of polymeric resin beads on to which the synthesis of a peptide is undertaken in a stepwise fashion with each amino acid being added sequentially to the peptide chain (Figure 15.1). In order to avoid the formation of side products each... 

FIGURE 27 15 Peptide synthesis by the solid phase method Ammo acid residues are attached sequentially beginning at the C terminus... 

A number of approaches may be adopted to achieve chemical synthesis of a peptide. The Merrifield solid phase synthesis method is perhaps the most widely used. This entails sequential addition of amino acids to a growing peptide chain anchored to the surface of modified polystyrene beads. The modified beads contain reactive chloromethyl (—CH2CI) groups. 

Scheme 5 Combined Solid-Phase and Solution Strategy for the Synthesis of Regioselectively Addressable Functionalized Templates (RAFT) with Four Orthogonally Protected Lysine Side Chains for Sequential Attachment of Four Different Peptide Sequences 171...

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