Synthetic Methods for the Preparation of Polypeptides

Studies of protein structures and their functions in nature or mode of actions, as in the case of enzymes, are only part of various investigations. Much effort is also put into syntheses of different polypeptide. Such polymers can actually be formed from mixture of various amino acids by simply heating them together. The products, however, are complex polymeric materials with random distribution of amino acids and do not resemble any naturally occurring materials. Base catalyzed ring opening polymerization reactions of N-carboxy-a-amino acid anhydrides also result in formations of polypeptides:

(for the mechanism of reaction see Chap. 5) [48]. Over the years, many polypeptides were synthesized by this reaction. These, however, were homopolymers of individual amino acids. Copolymerization leads only to block copolymers. Ability to form random copolymers with controlled sequences of amino acids, which would match naturally occurring proteins, appears to be beyond reach by this reaction [49, 50]. Duplication of naturally occurring polypeptides is needed, however, to understand the details of structures that lead to biological activities. One of the early works consisted of assembling 23 amino acids to form synthetic pig corticotropin [43]. The molecules were built stepwise [43]. One technique used in these syntheses is to protect the terminal amino nitrogen by forming protective derivatives that can subsequently be easily cleaved. This is often done by converting them to amide groups:

p-Toluenesulfonyl chloride is used in the same manner. It is also possible to form imides by reactions with phthalic anhydride:

The condensations can be carried out by a number of different techniques [26, 28]. A few of them will be shown below. One is to carry out amino acyl halide reactions:

The Schotten–Baumann reaction is used in many peptide syntheses. It is usually carried out in the presence of common bases to remove the halogen acid. Another reaction that is also utilized often is an acid azide condensation:

A unique way of coupling carboxylic acids with an amine group is by using an N, N-dicyclohexyl carbodiimide method. This can be illustrated as follows:

In addition to the above mentioned, rather painstaking, techniques of polypeptide syntheses, a very elegant technique was developed by Merrifield [53]. This solid phase peptide synthesis automates the reaction sequences. The method makes use of an insoluble cross-linked polymer substrate with pendant reactive groups for attachment of peptide chains. Chloromethylated polystyrene microgels are often used (see Chap. 9 for more discussions on the use of chloromethylated polystyrene for reactions of polymers). The chloromethyl moieties serve as the initiating sites for formation of the polypeptides:

A new amino acid with a protective group can now be added. The sequence of additions can be controlled and repeated many times to build up the desired polypeptide chain. Unwanted by-products of the syntheses are washed away or filtered off before each new step. This method lends itself so well to automation that automatic peptide synthesizers are now available commercially. One automatic peptide synthesizer was employed, for instance, in the synthesis of ribonuclease, an enzyme. In another instance, an enzyme, ferredoxin that consists of 55 amino acid residues was synthesized [26]. Most recent approaches to protein syntheses include use of templates for spontaneous self-assembly of multiple copies of a derivatized peptide [70]. The resultant structure, however, is not a conventional linear-chain protein. Instead, oxime bonds are formed between amino-oxyacetyl groups on the peptides and aldehyde groups on the template. The method is claimed to have many potential applications. Bode et al. [70] reported a new method for synthesis of peptide oligomers. The reaction creates aide linkages between a-keto carboxylic acids and N-alkylhydroxylamines.

اخر الاخبار

اخبار العتبة العباسية المقدسة

مدينة الفردوس تنظم برنامجًا ترفيهيًّا لأكثر من 260 يتيمًا من مؤسسة الفضل

العتبة العباسية المقدسة تطلق مسابقة ثقافية لطلبة جامعتي الكفيل والعميد

المجمع العلمي للقرآن الكريم يقيم محطات لتعليم القراءة الصحيحة في محافظة بابل

قسم الشؤون الفكرية ينظم دورة عن إعداد العروض التقديمية لطلبة المدارس في ذي قار

المزيد

الآخبار الصحية

للطاقة وحماية القلب.. ما "التوقيت الذهبي" لأكل المكسرات؟

دراسة تكشف فائدة القيلولة لمدة 45 دقيقة

اختيار الزبادي الأنسب.. قرار يحدد مسار صحتك

هل يعدّ الصيام المتقطع حلا سحريا لخسارة الوزن؟.. دراسة تجيب

المزيد

الآخبار التكنلوجية

"علي بابا" تكشف عن نموذج جديد للذكاء الاصطناعي

اختراق علمي جديد.. استشعار ضوئي يرصد "دلالات السرطان"

وكالة الإمارات للفضاء تعلن تمديد مهمة "مسبار الأمل" حتى 2028

ظاهرة مذهلة .. شهدها 2 بالمئة من سكان العالم فقط

المزيد

مواضيع ذات صلة

Polyalkanoates

Synthetic Methods for the Preparation of Nucleic Acids

DNA and RNA

Nucleic Acids

Chemical Modification of Proteins

Structures and Chemistry of Proteins

Proteins

Polyisoprene

Lignin

Derivatives of Cellulose

Regenerated Cellulose

Cellulose