Welcome to the on-line peptide community. Whether you are a scientist or researcher in the field of proteomics, from academia or industry, or simply interested in peptides and proteins, you have come to the right place.

What are peptides?

Peptides are organic compounds, like proteins, only shorter. Just like proteins, peptides are polymers consisting of amino acids. Amino acids in peptides are chained together with amino group of one amino acid bonding to carboxyl group of the next amino acid. This type bond is commonly referred to as peptide bond.

Peptides play important roles in living organisms. Most hormones, for example, are peptides.

Peptide Sequence

There are twenty naturally occurring or standard amino acids encoded directly within the universal genetic code. Peptides that naturally occur in living organisms are most often made of different combinations of these twenty amino acids.

Let us take adrenocorticotropic human hormone, for instance, it is a peptide that contains 39 amino acids. Following is its sequence.


Each letter in the sequence corresponds to one amino acid. In this sequence, from right to left, we see: F – which stands for Phenylalanine, then E – Glutamic Acid, then L – Lysine, etc, etc, until we reach S – Serine, at the very left.

As you can see, this sequence is one nice straight (though in real world a peptide does not have to be straight, it can and will twist, turn, and take many conformations) chain of amino acids. Peptides like these are called linear peptides.

Peptide Termini

A liner peptide molecule has two ends, these are called termini. The one on the right is carboxyl end or C-terminus; the one on the left is amino end or N-terminus.

In our example sequence above the C-terminus is free acid, and the N-terminus is free amine. These are sometimes called open termini, and if the peptide sequence does not explicitly specify other types of termini, it is assumed that the peptide has open termini.

We can explicitly specify open termini when writing sequences. Following are different ways of writing a peptide sequence (fragment of the peptide from our first example), with the same free acid on the right and free amine on the left.





All four notations above refer to the same peptide with the same free termini. The first notation omits any indication of the termini, free termini are the default.

In the second notation we see “-OH” after the Methionine (M) amino acid, this is the “-OH” that would go away if there was another amino acid to the right of the M. Similarly, in the third notation we see ”H-“ before the leftmost Serine (S) amino acid; if there was another amino acid to the left of the S, that “H-“ would also go away to create the peptide bond between the S and the new amino acid.

Finally, the last notation emphasizes the functional groups at the peptide molecule termini; carboxyl group at the right and primary amine group at the left.

Amidation and Acetylation

The opposite of free termini is capped termini. We can cap the C-terminus of a peptide by amidating it.


Above is the peptide with C-terminus amide. To emphasize the carboxamide functional group, we can write the same peptide as follows: SYSM-CONH2. Note that in addition to the carboxamide group at a peptide capped C-terminus, the two standard amino acids, Asparagine (N) and Glutamine (Q), feature a carboxamide group on their side chains.

Capping the N-terminus can be done with acetylation.


Above is the peptide with acetyl on N-terminus.

Linear peptides can be capped both on C and N-termini.


Above is the peptide both amidated and acetylated. Amidation and acetylation generally make peptides more stable and often alter biologic activity.

Terminus Modifications

Besides amidation and acetylation, peptide termini, especially the N-terminus, are convenient places to attach other molecules or labels to peptides. Popular peptide terminus modifications include: Biotinylation, attaching different kinds of Fluorescein or Rhodamine dyes, conjugation to KLH, BSA, and other proteins; directly or using single or multiple aminohexanoic acid, polyethylene glycol and other spacers.

C-terminus and N-terminus of a peptide may even be connected together, forming a head-to-tail cyclic peptide.

Internal Peptide Modifications

In addition to the termini, internal peptide structure can also be modified. Various spacers can be inserted between amino acids. Some amino acids inside the peptide can be phosphorylated, methylated, acetylated; various chemical groups can be attached.

Side Chains

The side chain of the standard amino acid Lysine (and of non-standard Ornithine) contains amino group that can be used to form isopeptide bonds – amide bonds branching from the main chain of the peptide. Lysine, thus, can be conveniently used to place various tags or additional chains of amino acids at the C-terminus, or anywhere else in the peptide.

Two of the standard amino acids, Aspartic Acid (D) and Glutamic Acid (E), contain a carboxyl group on their side chains. Creating an amide bond between the amino group on the side chain of a Lysine and the carboxyl group on the side chain of an Aspartic Acid or a Glutamic Acid is another way to create a cyclic peptide. The bonds created this way are often referred to as lactam bonds or lactam bridges.

Disulfide Bridges

Another interesting amino acid is Cysteine; its side chain mercapto (thiol) group can react with mercapto group of another Cysteine forming a disulfide bridge or disulfide bond. These disulfide bridges can exist between Cysteines at different positions within a peptide; these peptides are also often called cyclic peptides in addition to the head-to-tail cyclic peptides and cyclic peptides with lactam bonds we discussed earlier.

Below is the sequence of the Urotensin II, human peptide.


Counting from left to right, this peptide has Cysteines at positions five and ten, these form a disulfide bridge, and the notation at the left of the sequence tells us about it.

A peptide may have more than one pair of Cysteines forming disulfide bridges. The a-Conotoxin MI peptide (a fish hunting cone snail toxin) below is an example of that.

[Cys3-Cys8, Cys4-Cys14] GRCCHPAC­GKNYSC-NH2

The third and eighth position Cysteines form a disulfide bridge, as do the ones in the fourth and fourteenth positions.

Just because a peptide contains Cysteines they do not have to necessarily form disulfide bridges (though in nature they often do). Do you know what the difference between curly and straight hair is? The proteins in curly hair have more disulfide bridges; chemical hair straightening works by breaking up those disulfide bridges.

In addition to intramolecular disulfide bridges, disulfide bridges may also form intermolecularly between identical or non-identical peptides.

More about peptides.