Proteins and Amino Acids structure

What are proteins?

Polymers or long chains of amino acids

Can be described as peptides, polypeptides or proteins depending on length

How are they made?

Synthesised in cells through translation of RNA

Chemical synthesis is also possible

manual- lab

automated- machine

Examples of proteins

Proteins can be natural ligands e.g. met enkephalin

( natural painkillers)

Proteins can be drugs e.g. monoclonal antibodies, insulin ( known as Biologics )

Proteins are the major type of drug target

Why do proteins matter?

They are important in how drugs work

eg .

-receptors, they change shape

-enzymes- require chemical reactions

-nuclear receptors- DNA , protein synthesis, longer hours

- ion channels - really fast , =transport of essential ions

How do we draw and represent molecules?

SKELETAL FORMULA

-molecules aren't flat ,3d

-no need to draw all hydrogens ,only draw functional groups

What is the primary structure of a protein ?

The order/sequence of amino acids

The proteins - have a backbone -which joins the aa

residues- side chains, reponisable for binding =decides the type/strenght of bonding interactions within drug molecules

makes amide bonds =rigidity

Name the functional group of each of the residues

thiol- represents sulfa

alkyl group-methyl groups

phenol- benzene,alcohol

arene-benzene

What is secondary structure?

Hydrogen bonds between peptide backbones

Areas of order within protein structure

Two main types α-Helix and β-sheet

NOTE- ordering = more rigidity ,caused by h-bonds

Describe alpha- helix and its properties?

Coiling of chains

Hydrogen bonds between amides

Residues point outwards- less interaction

less steric interaction between them

stabilise the structure

Describe Beta pleated sheet?

layering of chains

Can run in either direction

parallel or anti parallel

Held together with hydrogen bonds between amides in different layers

Residues point outwards

less steric interaction between them

stabilise the structure

What is tertiary structure?

Overall 3d shape of a protein - THE MOST IMPORTANT FOR DRUG ACTION

Achieved by additional interactions between side chain residues

Folding of peptide chain brings diverse amino acids into close proximity ⇒ binding site

What is the importance of tertiary structure in drug action ?

Folded up decides where the drug attaches /binds because it binds to non- neighbouring amino acids

What is Quaternary structure?

-Proteins that are made up of multiple proteins e.g. haemoglobin

-Individual proteins called subunits

-Structure caused by surface interactions between residues on the subunits

How many amino acids are commonly found in nature?

20 amino acids   

-11 made in the body ,9 from our diet ( all are alpha amino acids)

What do Residues and functional groups determine?

-size

-shape

-the type of bonds that can be formed (reactive bonds- covalent ..,Interactive bonds- non permanent bonds hydrogen,ionic bonds)

What is the difference between Alpha amino acid and Beta Amino acids?

Alpha- One carbon between the functional groups

Beta- 2 carbons between them -useful when designing drugs to stabilise the structure into peptides

NOTE- Synthetic amino acids can be incorporated into drugs to increase stability

What are the groups Amino acids can be sorted into ?

-for drug interaction

  -bond forming ability is most useful

What are the Amino acids that are capable in forming covalent bonds  and what do  have in common ?

Threonine, Thr 

Cysteine, Cys

Serine, Ser

Tyrosine, Tyr

all have  alcohol and thiols they can lose hydrogens ,turned into a nucleophile , to form a covalent bond (STRONGEST BONDS)

Note - Directional – between two molecules

Why are the amino acids formed by covalent bonds important?

Most important in enzyme interactions/inhibitors  with drugs

In receptors cause receptor block- permanently changed can’t be reversed  – don’t want covalent bonds

What are the amino acids that are capable in forming ionic bonds and what do they have in common?

Glutamic acid, Glu,

Lysine, Lys

Arginine, Arg

Histidine, His

Aspartic acid, Asp

common - have carboxyl acid groups, amine group ( base) ,can lose or gain a hydrogen involved in ionic interaction

NOTE- acid = - ve lysine= + ve

Why are amino acids that form ionic bonds important ?

Really important in all drug receptor and drug enzyme interactions

Allow strong binding but also dissociation

STRONG BUT CAN BE REVERSED

What are the amino acids  that can form Hydrogen bonds?

Serine, Ser

 Threonine, Thr

 Cysteine, Cys 

Tyrosine, Tyr 

Aspartic acid, Asp

 Glutamine, Gln

 Histidine, His. 

Tryptophan, Trp. 

 NOTE - Hydrogen bonds are weaker and usually require lots for strength

What are the amino acids that are capable of forming Hydrophobic interactions?

Alanine,ala

valine,val

leucine,leu

Isoleucine,ile

Phenylalanine,phe

Proline,pro- cyclic compound residue in a circle tertiary amine- provides more stability in a protein ,more rigid

Methionine ,Met

common- alky ,aryl chains

Note- WEAKEST

Not directional – multiple amino acids interacting so they have a hydrophobic surface

What bonds does Glycine form ?

Glycine  -   nothing  , used for structure , spacer between other groups , no residue so no interactions

What type of bonds does Asparagine form 

ionic, hydrogen,

DEPENDS ON THE PH