Peptides

What is the longest English word you can spell using the one letter abbreviations of the 20 genetic amino acids? What about the three letter abbreviations? What would the resultant peptides look like?

—Kira (Lysine-Isoleucine-Arginine-Alanine) Guth

These are the 20 amino acids that appear in our genetic code:

Since the 20 amino acid abbreviations include most of the common letters, you can spell almost anything you want with them.

There are lots of novelty "longest words" in English. Since there's no standard English dictionary, the actual longest word is just a question of what we're willing to let someone get away with. We all like Julie Andrews, so we usually allow "supercalifragilisticexpialidocious."[1]Holy crap, I spelled that right on my first try. Many people have memorized other novelty words like "antidisestablishmentarianism."

The longest words that a regular English speaker might hear or use in casual conversation is probably uncharacteristically (20 letters),[2]Tied with compartmentalization, indistinguishability, and internationalization. and the longest "normal" word without getting too cute about prefixes[3](and sounding precocious) might be deinsitutionalization (22 letters).[4]Tied with counterrevolutionaries and electroencephalography. overintellectualization is arguable at 23.

None of those 20-plus-letter words can be spelled with the 20 allowed amino acid letters. The longest reasonably common word that can be spelled with those letters is probably interdepartmentally (19 letters), although it again comes down to what you consider "common".

How about the three-letter abbreviations?

The three-letter amino acid abbreviations turn out to be surprisingly tough to make words from. A few of them are words themselves (like his), but there's only one word that can be made by combining them: SER•VAL (SV, serine-valine), a type of cat native to Africa.

What would these peptides look like?

Well, that's hard to answer without synthesizing them. The peptide INTERDEPARTMENTALLY is long enough that it almost certainly doesn't appear in any existing genetic sequence, and SV (serval) is short enough that it's common everywhere and doesn't really mean much on its own.

But what's the longest word that does appear in a known peptide/protein[5]A peptide is a short sequence of amino acids, while proteins are longer sequences made up of peptides, but the line between them is pretty arbitrary. sequence?

There are some tools for searching known proteins, including PepBank, UniProt, and PeptideDB. By downloading and searching through some of these peptide databases, we can look for English words spelled out using amino acid abbreviations.

It's easy to find four- or five-letter words in these peptide sequences, and you can come across a few seven-letter ones here and there. One random peptide sequence from the 11th chromosome of the human genome, MADSVKTFLQDLARMLESSKRERSSVEEGQVVSWHREEPRV, contains the seven-letter word armless (UniProt entry).

You also, occasionally, come across eight-letter words:

• GRISETTE, a type of mushroom, which appears in a brain-related NXPE family member 3 precursor[6]Don't ask me. protein.

• DATELESS, which appears in a protein involved in controlling cell growth which may be important in cancer.

• REVERSAL, which appears in the sequence on chromosome 1 which encodes the protein rootletin. Rootletin is a fibrous protein found in the base of cilia, the little hairlike fibers that stick out of our cells. These fibers (also called flagella when there are few of them) are sometimes used to push things around; cilia in our lungs help push out dirt and debris. These gadgets can also enable individual cells to swim; this is how sperm cells and ulcer-causing bacteria push themselves around.

The universe of proteins is enormous, and there are certainly longer words lurking out there somewhere, waiting to be found. If you find a peptide containing a longer word, you could be eligible for a Nobel Prize—but only in the sense that anyone who's not dead is technically eligible.

Lastly, let's return to Kira's question. In her email, Kira gave her name as Lysine-Isoleucine-Arginine-Alanine, or KIRA. I searched for this sequence in a few peptide databases, and I have some good news, some bad news, and some gross news.

The gross news is how the sequence was found. Strep throat, and many common skin infections, are caused by Streptococcus bacteria. In 1995, researchers isolated several proteins produced during these infections, looking for possible targets for antibodies. One of the proteins they found was WYSLNGKIRAVDVPK, or GKIRAV for short.

The bad news is that the researchers filed a patent which includes this sequence. The patent, published in 1999, gives the researchers exclusive control over this protein. If Kira wants to mess around with the protein, she could—in theory—be sued.

The good news is that in 2013, the Supreme Court struck down this type of gene patent. The case, Association for Molecular Pathology v. Myriad Genetics, Inc., involved the patents protecting tests for genetic cancer risk. That means Kira is totally free to produce as much WYSLNGKIRAVDVPK as she wants.

But I would still advise against it.