The near future releases " medicine of medicaments of chemical synthesis polypeptide learns to study instructor principle (ask for an opinion to stalk of grain) " in mention: In solid photograph synthesis, colophony serves as indispensible stock, its quality can affect polypeptide medicaments quality directly, should offer resinous origin, quality standard and examine report, right resinous rub the stability situation that Er replaces the coefficient, coefficient of expansion in different dissolvent, place to fall with synthetic condition give specification. Because lack effective token,the method is mixed and of specific aim charge a means character, do not recommend the colophony that carries amino acid to be linked together with peptide catenary C to serve as initiative stock. This shows, although colophony falls not to participate in the structure that makes final API in some circumstances, but also should undertake study adequately to its. I introduce the commonly used colophony in synthesis of polypeptide solid photograph simply with everybody today. One, above all we should understand a few first about resinous important parameter: Cross-linking is spent, eye number, replace degree, the swellbility in different dissolvent. Cross-linking spends: It is with PS colophony exemple, its colophony ball is the cross-linking agent that adds certain amount in polystyrene 2 vinyl benzene, react through polymerization and become. The affiliation of 2 vinyl benzene measures cross-linking agent even if cross-linking is spent (DVB) , optimal cross-linking spends colophony for 1% , taller cross-linking is spent bring about colophony swellbility to drop, however inferior cross-linking is spent can reduce colophony to bilge in dissolve the mechanical stability below condition. The colophony that will tell city to make work commonly is cross-linking is spent for the most part for of 1% . Eye number: The size of colophony ball, colophony of general city carry out looks for 100-200 (average diameter is 75-150μm) , the condition of aggregate reaction can affect the size of colophony ball. Replace degree: Every gram colophony laded how many fine long hair rub the active reaction of Er dot, the unit is Mmol/g. Notable is the Wang-resin that general city makes work, CTC-resin in one's hand hind, we can lade in the lab the first amino acid, but these two kinds of resinous amino acid lades lead and cannot achieve 100% , should determine afresh after this so replace degree. Swellbility: Colophony bilges in the dissolve in different dissolvent ability, the unit is Ml/g. The colophony that general city makes work in one's hand hind, before we are used, need to undertake with solvent dissolve bilges, good dissolve bilges can increase reactant to enter a chance of the dot. Ketone of alkyl of methylic pyrrole of DCM, DMF, N- is commonly used benign colophony dissolve bilges solvent. 2, a few kinds of commonly used colophony introductions 1, the commonly used colophony in synthesis of photograph of Wang-resin polypeptide solid, functional radical group is hydroxyl, the first amino acid passes ester key and resinous LInker is linked together. Accordingly occasionally couplet condition should compare acyl amine key is acuteness, need DMAP catalysis. Because DMAP is alkalescent stronger, the amino acid that particularly easy pass the time in a leisurely way comes back (Cys, his) does not suit to lade at Wang-resin, recommend use CTC-resin right now. In addition, when Gly, Pro is being contained in carrying 2 peptide when Wang-resin carbon, still should notice DKP deputy reaction, mechanism sees a picture 2. After N- carries amino acid to take off Fmoc bare piece amino, to the acyl in front amine bolts or ester bolts close nucleus is attacked, the part that gets an effect falls off from colophony with the form of 2 ketone piperazine, bring about finally close rate drop. There is Gly in before be being carried when C- two amino acid, pro, n- alkyl amino acid, the meeting when alternant D/L amino acid quickens this pair of reaction. When the L of use stationary phaseWhen Inker type bolts for ester, this kind of deputy reaction is most severe, because compared with amino, hydroxyl is one stronger leave base round. Use CTC-resin can control this pair of response. The L of Wang-resinInker is stabler, need splitting decomposition of high concentration TFA. Splitting decomposition falls in condition of high concentration TFA, the L of Wang-resinInker may produce irregular splitting decomposition to arise ionic 1, if Trp incomplete exists in peptide catenary base, ion may attack Trp the impurity of the unripe M+106 of indole annulus induced labor of catenary of incomplete radical side, mechanism sees a picture 3. Below normal circumstance, the L of Wang-resinInker ruptures in A place, but should contain in peptide catenary a few take off the side catenary that divide hard when protective radical (the side catenary Pbf that is like Arg, the carboxyl of DOTA annulus the) such as protective radical TBu, must use stronger cut condition, at this moment the L of Wang-resinInker produces irregular splitting decomposition likely, rupture at the same time in A and B place, generation ionic 1, this kind of ionic and special appearance attacks Trp side catenary easily. Use CTC-resin is OK and complete avoid reacts this pair, if must use Wang-resin, can drop cut temperature, shorten cut time will control this pair of response.
