Combined solid‐phase and solution approach for the synthesis of large peptides or proteins
In the synthesis of large peptides or proteins, highly homogeneous segments are indispensable for a convergent strategy either on a solid‐phase resin or in solution. Employing Boc/Bzl chemistry to prepare fully protected segments with a free α‐carboxyl group from the solid support, base‐labile linkers are profitable for practical peptide synthesis since they require no special equipment. For this purpose, an N‐[9‐(hydroxymethyl)‐2‐fluorenyl]succinamic acid (HMFS) linker was adopted. Consequently, there must be high compatibility between the protecting groups of the segment and the anchoring group which is cleavable by treatment with morpholine or piperidine in DMF. Instead of using the 2‐bromobenzyloxycarbonyl (BrZ) group for the Tyr residue and the formyl (For) group for the Trp residue, both of which are the most susceptible protecting groups under these base‐catalysed conditions, the base‐resistant 3‐pentyl (Pen) and cyclohexyloxycarbonyl (Hoc) groups were introduced to the respective side‐chain functional groups. By applying the present strategy, the authors were able to rapidly synthesize homogeneous protected segments for use in the subsequent segment coupling in solution. In the present paper, the utility of the combined solid‐phase and solution approach is demonstrated by synthesizing muscarinic toxin 1 (MTX1) which binds to the muscarinic acetylcholine receptors. Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd.
Comparison of procedures for directly obtaining protected peptide acids from peptide‐resins
The preparation of small‐sized protected peptide acids related to cholecystokinin and gomesin was attempted using peptide‐Kaiser oxime resins (KOR) as starting materials. For comparison, peptide‐2‐Cl‐trityl resin (CLTR) was also employed. While peptide detachment from KOR was achieved through the oxime ester bond hydrolysis mediated by DBU, hydroxide ion or Ca+2 ion, peptide release from CLTR was accomplished through acid‐catalysed hydrolysis of the peptide‐resin ester linkage. Amino acid analysis of the peptide‐resins before and after peptide release allowed the calculation of the reaction yields. RP‐HPLC and LC/ESI‐MS of the resulting crude peptides allowed estimation of their quality. The data collected indicated that: (i) among the procedures used for peptide displacement from KOR, the one employing DBU was the most efficient since it furnished all model protected peptide acids with the highest quality in a very short time; (ii) although slow, Ca+2‐assisted peptide detachment from KOR was selective and was suitable for generating high‐quality protected peptide acids containing up to five residues; (iii) even though the protocols employed for peptide release from CLTR have shown to be appropriate, the one employing 1% TFA/DCM was the most productive; (iv) in terms of product quality, DBU‐catalysed peptide detachment from KOR was similar to TFA‐catalysed peptide release from CLTR although the latter was more productive. These findings are relevant to peptide chemists in general, but especially to those interested in preparing acyl donors for convergent peptide syntheses by the t‐Boc chemistry. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Metallurgical Process Engineering
The "material of choice" - steel.- Uprising of China's steel industry.- Process manufacturing industry and process engineering.- Engineering science in steel manufacturing process.- Analysis and integration of metallurgical manufacturing process.- Multi-dimensional mass flow control for metallurgical manufacturing process.- Time factors in steel manufacturing process.-Operating dynamics in the production process of steel plant.- Structure and mode of steel plant.- Steel plant and environment.