An Introduction to Medicinal Chemistry PDF

# An Introduction to Medicinal Chemistry ## Chapter 3 ### Drug Targets ### Proteins *Salih Al-Jabour, Dr.rar.nat* *Pharmacy Department* *AlQuds University* *Jerusalem, Palesinte* ## 1. The Building Blocks for Proteins - Proteins are macromolecules made up of amino acid building blocks. - There ar...

# An Introduction to Medicinal Chemistry ## Chapter 3 ### Drug Targets ### Proteins *Salih Al-Jabour, Dr.rar.nat* *Pharmacy Department* *AlQuds University* *Jerusalem, Palesinte* ## 1. The Building Blocks for Proteins - Proteins are macromolecules made up of amino acid building blocks. - There are 20 common amino acids in human proteins. | | | | | | ---------- | ---------- | ----------- | ----------------- | | H | H | O | R group | | | | | | | H | H | | | | N | C | C | α-carbon | | | | | | | H | H | | | | | R | | | | | | O | | | | | | | | | | | | | | | O | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 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| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - **Zwitterions**: formerly called a dipolar ion, is a molecule with two or more functional groups, of which at least one has a positive and one has a negative electrical charge and the net charge of the entire molecule is zero. - **Cation:** ${NH_3}^+$ $R - C - COOH$ $H$ - **Zwitterion:** ${NH_3}^+$ $R - C - COO^-$ $H$ - **Anion:** $NH_2$ $R - C - COO^-$ $H$ ## Amino Acids - **Nonzwitterions:** $H$ $H$ $N$ $C$ $C$ $H$ $H$ $R$ $O$ $O$ $H$ - Non-ionized form of amino acids - **Zwitterions:** $H$ $H$ ${NH_3}^+$ $C$ $C$ $H$ $O$ $O$ $O$ $H$ $R$ - Ionized form of amino acids (zwitterion). - Amino acids are **chiral molecules** (except **glycine**, R=H). - **Chiral Center:** $COOH$ $^*$ $H - N$ $C$ $R$ $H$ $NH_2$ - **Mirror Image:** Nonsuperimposable mirror images - **Enantiomers:** Isomers L (R), D (S) ## General Amino Acid Features ### Chirality and the R, S System *H<C<N<O* | R-clockwise | S-counterclockwise | |--------------|------------------| | | | | | | | | | | | | | | | | | | | | | | | | - **Mirror:** - $COOH$ - $^*$ - $H_2N$ - $C$ - $R$ - $H$ - **L-amino acid** - **R-isomer (L)** *FISCHER DIAGRAM* - $COOH$ - $^*$ - $H$ - $C$ - $R$ $NH_2$ - **D-amino acid** - **S-isomer (d)** - Each amino acid has an **identical head group**. - Amino acids are **chiral molecules**. (except **glycine**, R=H) - Only **L-amino acids** are present in human biochemistry. - The **L-amino acids** are **R-enantiomers**. (except cysteine; $R = CH_2SH$) ## Codes for Amino Acids | NAME | 3 LETTER CODE | ONE LETTER CODE | |--------------|----------------|-----------------| | Alanine | Ala | A | | Arginine | Arg | R | | Asparagine | Asn | N | | Aspartic acid | Asp | D | | Cysteine | Cys | C | | Glutamic acid | Glu | E | | Glutamine | Gln | Q | | Glycine | Gly | G | | Proline | Pro | P | | Serine | Ser | S | | Tyrosine | Tyr | Y | | Histidine | His | H | | Isoleucine | Ile | I | | Leucine | Leu | L | | Lysine | Lys | K | | Methionine | Met | M | | Phenylalanine | Phe | F | | Threonine | Thr | T | | Tryptophan | Trp | W | | Valine | Val | V | ## A Guide to the Twenty Common Amino Acids Amino acids are the building blocks of proteins in living organisms. There are over 500 amino acids found in nature - however, the human genetic code only directly encodes 20. 'Essential' amino acids must be obtained from the diet, whilst non-essential amino acids can be synthesised in the body. **Chart Key:** - Aliphatic - Aromatic - Acidic - Basic - Hydroxylic - Sulfur-containing - Amidic - Non-Essential - Essential - Alanine - Glycine - Isoleucine - Leucine - Proline - Valine - Phenylalanine - Tryptophan - Tyrosine - Aspartic acid - Glutamic acid - Arginine - Histidine - Lysine - Serine - Threonine - Cysteine - Methionine - Asparagine - Glutamine ## Willie Taylor's Scheme | | | |---------------------------|------------------------------------------------------| | **Hydrophobic** | Glycine (Gly,G) | | | Proline (Pro, P) | | | Alanine (Ala, A) | | | Valine (Val, V) | | | Leucine (Leu, L) | | | Isoleucine (Ile, I) | | | Methionine (Met, M) | | **Polar** | Phenylalanine (Phe, F) | | | Tryptophan (Trp, W) | | | Serine (Ser, S) | | | Cysteine (Cys, C) | | | Threonine (Thr, T) | | | Tyrosine (Tyr, Y) | | **Charged (-)** | Glutamine (Gln, Q) | | | Asparagine (Asn, N) | | | Glutamic Acid (Glu, E) | | | Aspartic Acid (Asp, D) | | **Charged (+)** | Histidine (His, H) | | | Lysine (Lys, K) | | | Arginine (Arg, R) | ## 2. The Primary Structure of Protein - **Amino acid (1)** $H$ $H$ $N$ $C$ $C$ $H$ $R_1$ $O$ $O$ $H$ - **N-terminus** **C-terminus** - **Amino acid (2)** $H$ $H$ $N$ $C$ $C$ $H$ $R_2$ $O$ $O$ $H$ - **Peptide Bond** $H$ $H$ $N$ $C$ $C$ $H$ $R_1$ $O$ $H$ $H$ $N$ $C$ $C$ $H$ $R_2$ $O$ $O$ $H$ - **Dipeptide** - **Water** $H_2O$ - $H$ $H$ $H - N$ $^*$ $C - C - OH$ $O$ $R$ $H$ $H$ $H - N$ $^*$ $C - C - OH$ $O$ $R$ - **Peptide Bond** $H$ $H$ $H - N$ $^*$ $C - C - N$ $O$ $H$ $C - C - OH$ $O$ $R$ $R$ - **+** $H_2O$ ## 3. The Secondary Structure of Protein - **R** 1.24 A 1.46 A 1.53 A **C** **C_α** - **C<sub>