Solid Phase Synthesis

Abstract

T HE PROTEINS, AS THE GEEK RooToF THEiO NAME implies, are offirst rank in living system, and their smalle relatives, the peptides, have now also been discovered to have importnt roles in biology. Among their m s are many of the hormones, rekasing facrs, growth factors, ion carriers, antibiotics, toxins, and neuropcptides. My purpose tday is to describe the chemical synthesis of peptides and pins dto discuss the useofthe synthcetic approach to answer various biolo l questions. The stry begins with Emil Fisdwr (1) at the tur ofthis century when he synthesized the first peptide and coined the name. The general chemical requirements were to block the arboxyl group of one amino acid and the amino group of the second amino acid.Then, by activatin of the free carboxyl group the peptie bond could be formed, and sclectivc removal ofthe two protecting groups would Icad to the free dipeptide. Fischer himself was never able to find a suitable reversible b ing group for the amine funcion, but his sudent Max Bergmann, t with Leonidas Zervas, was successfl (2). Their design ofthe carbobenzoxy group ushered in a new era. When I began working on the sis of peptides many years later, this same general scheme was universally in use and was very cffective, having led, for example, to the first synthesis of a peptide hormonc by du Vigneaud in 1953 (3). It soon became dar to me, howcevr, that such synteses were difficuk and time consuming, and that a new approach was needed if lar numbes of peptides were required or iflarger and more complex pkptdes were to be made. Synthesis on a Solid MatrixOne day I had an idea about how the goal of a morc efficent synthesis might be achieved. Thc plan (4) was to assemble a pcptidc chain in a stepwise manner while it was a A atone end to a solid support. With the growing chain covaently anchored to an insolublc matrix at all stages of the synthsis, the peptidc would also bc compktely insoluble and, fiurhermore, would be in a suitable physical form to permit rapid filtration and washing after completion of each ofthe synetic reactions. be in it pepds in the synthesis would thus be purified by a vcry simple, rapid prcedure rather than by the usual tedious ystizai me s. When a mutistep process, such as the p on of a long polyeptide or protein, is contemplated the saving in time, effort, and materials could be very large. Thc fact that all of the stps jt described are hetcrogeneous reactions between a solubk reagent in the liquid phase and the growing peptid chain in the insoluble solid phase led to the introduction of the name "solid phase peptid synthesis."The general scheme for solid phase synthesis is oudined in Fig. 1. It begins with an insolublc particle (large crcles), which is functioalized with a group, X. The first monomer unit (sml crcles) is blockd at one end and at the reactve side-chain groups (black dots) and anchored to the support by a stable covalent bond. The a prtcting group is then renoved and the second monomer unit is added to the first by a suitable reaction. In a similar way th...

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Characterization of two antigenic sites recognized by neutralizing monoclonal antibodies directed against the fusion glycoprotein of human respiratory syncytial virus

“…The peptides indicated in Table 2 were synthesized according to the sequence of the Long strain F protein in an Applied Biosystems 430 instrument, using the solid-phase technology and t-Boc chemistry developed by Merrifield (1986). The peptides were cleaved off the resin with trifluoromethyl sulphonic acid, and purified from protecting groups and scavengers by Sephadex G-25 chromatography.…”

Chemoenzymatic Synthesis of Polypeptides for Use as Functional and Structural Materials

“…In contrast, CPDY is characterized as an exopeptidase that typically cleaves only amide bonds at C-termini. Therefore, CPDY-catalyzed polymerization avoids the hydrolysis of the polypeptide backbones of pre-existing polypeptides, resulting in efficient suppression of the broadening of the molecular weight distribution of the products that Methyl, [49,54] ethyl, [50][51][52][53][54][55][56] benzyl [54] Proteinase I, [49] papain (13)(14)(15)(16)(17)(18) [50][51][52][53][54][55][56] Glycine Methyl, [54] ethyl, [49,51,54,55] benzyl [54] Proteinase I, [49] papain (10)(11)(12)(13)(14)(15)(16)(17)(18)(19) [51,54,55] l-Leucine…”