Carboxyl Groups

A carboxyl group has the formula  COOH. Among compounds that have a carboxyl group are carboxylic acids. A carboxyl group shows relatively weak acidity. Many carboxylic acids are found in nature as free acids or in the form of esters, amides, or salts. Biologically important acids are those found in the metabolic pathways of glycolysis, fatty acids, amino acids, and so on. A carboxylic acid reacts with a base to form a salt and can be reduced to an aldehyde and an alcohol. A carboxylic acid forms an ester with an alcohol, an amide with an amine, and an acid anhydride with an carboxylic acid. Carboxyl groups are not very reactive, and some catalyst or activation processes are required for their reactions.

There are three kinds of carboxyl groups in proteins, the C-terminal a-carboxyl, the b-carboxyl of aspartic acid, and the g-carboxyl of glutamic acid. They have intrinsic pK_a values of 3.8, 4.0, and 4.4, respectively. Carboxyl groups are often employed as catalytic groups in enzymes, and they often play critical roles in ligand binding. Thus, carboxyl groups are important in protein chemistry.

 1.  Chemical Modification of Carboxyl Groups in Proteins

Esterification and amidation are the usual chemical modifications of carboxyl groups (1). Carboxyl groups in proteins are esterified by treating the dry protein with methanol-HCl. However, this method is drastic and not suitable for selective modification of carboxyl groups. Trialkyloxonium salts, such as triethyloxonium tetrafluoroborate, are commonly used for mild esterification of carboxyl groups in proteins (2). Diazoacetyl compounds, such as diazoacetamide, methyl diazoacetate, and N-diazoacetylglycinamide, react with carboxyl groups at acidic pH to form esters. Other reagents, such as acid halogen compounds and ethyleneimine have also been used to esterify the carboxyl groups in proteins.

Carboxyl groups are amidated with simple amines after activating the carboxyl groups with water soluble carbodiimides, such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) [I]. At pH 4.75 to 5, the reaction proceeds as in Scheme 1. Exhaustive amidation is achieved by using high concentrations of both amine (1 M) and EDC (0.1 M) at pH 4.75 under denaturing conditions (3). Limited amidation is possible using low concentrations of amine (0.1 M) and EDC (2.6 mM) under mild conditions at pH 5.0 (4). Isoxazolium salts, including Woodward's Reagent K (2-ethyl-5-phenylisoxazolium 3′-sulfonate), can be used in the place of EDC at pH 3 to 5. Amidation is also achieved by ammonolysis of the esters in liquid ammonia at –55°C. In this case, selective amidation is possible starting with a selectively esterified protein (5).

References

1. T. Imoto and H. Yamada (1989) In Protein Structure: A Practical Approach (T. E. Creighton, ed.), IRL Press, Oxford, U.K., pp. 247–277. 

2. S. M. Parsons et al. (1969) Biochemistry 8, 700–712. 

3. T.-Y. Lin and D.E. Koshland Jr. (1969) J. Biol. Chem. 244, 505–508. 

4. H. Yamada et al. (1981) Biochemistry 20, 4836–4842. 

5. R. Kuroki et al. (1986) J. Biol. Chem. 261, 13571–13574.

اخر الاخبار

اخبار العتبة العباسية المقدسة

العتبة العباسية المقدسة تنظّم مسيرات عزائية لإحياء ذكرى عاشوراء في نينوى

قسم الشؤون الفكرية يحيي ذكرى استشهاد الإمام الحسين (عليه السلام) في القارة الإفريقية

قسمُ التربية والتعليم يقيم مجلسه العزائي السنوي بذكرى عاشوراء

معهد القرآن الكريم النسوي يُقيم مجلس عزاء حسيني إحياءً لذكرى عاشوراء

المزيد

الآخبار الصحية

تناول الجبن.. مفيد للجسم أم خطر يهدد صحتك؟

طبيبة أسنان تحذر.. لا تتجاهل هذه العلامة بعد التنظيف

يجب أن تأكل المزيد من الشمام هذا الصيف.. إليك السبب ؟

تأثير صحي كبير.. كم بيضة يجب أن تتناول يوميا؟

المزيد

الآخبار التكنلوجية

أداء خلايا البيروفسكايت الشمسية تحت الماء قد يزيد كفاءة تحويل الكهرباء

مسافة الأمان: أساس القيادة الآمنة وتجنب الحوادث

هل القيادة السريعة تعني استهلاك اكثر للوقود؟

لماذا يعتبر كوكب المريخ غير صالح للحياة؟

المزيد

مواضيع ذات صلة

Site for Cro Repression and CI Activation

Chronology of Becoming a Lysogen

N Protein and Antitermination of Early Gene Transcription

Spontaneous Mutations in bacteria

Mechanisms of Gene Transfer in Bacteria

Phage Replication

Genotoxicity Through Potential Off-target Nuclease - Induced Double - Strand Breaks

A Broad Range of Genomic Changes by Homologous Recombination–Mediated Genome Editing

Early Transcription of Genes N and Cro

Lambda’s Relatives and Lambda Hybrids

The Genetic Structure of Lambda

The Physical Structure of Lambda