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Short answer
“Conjugate protein” is used for two different things. In biochemistry, a conjugated protein is a polypeptide joined to a non-amino-acid part called a prosthetic group, such as the heme in hemoglobin. In biotechnology, a protein conjugate is a protein covalently linked to another molecule, such as a drug, a polymer or a carrier-bound polysaccharide. Check which meaning a source intends before using the term.
Definition and scope
The two meanings share a word but not a mechanism,, so it helps to keep them apart.
Conjugated proteins (the biochemistry sense)
A chemistry course text from Brevard College on LibreTexts says the non-amino-acid portions of conjugated proteins “may consist of metals, lipids, sugars, phosphate” or other types of molecules, and that these components are referred to as prosthetic groups. Its example is hemoglobin, a globular conjugated protein with heme as the prosthetic group. These groups are part of the protein as it occurs in the cell.
Protein conjugates and conjugating proteins (the bioconjugation sense)
Sornay and colleagues (Royal Society Open Science, 2022) define bioconjugation of proteins as “the creation of a covalent link between a protein and any other molecule”. Here a person chooses the partner molecule and the chemistry. “Conjugating proteins” and “protein conjugation” name that act, and “protein conjugates” name the product.
How the two senses compare
| Question | Conjugated protein (biochemistry) | Protein conjugate (bioconjugation) |
|---|---|---|
| What is attached | A prosthetic group such as heme, metals, lipids, sugars or phosphate (LibreTexts, Brevard College) | “Any other molecule” (Sornay et al., 2022) |
| Who joins the parts | The organism, as part of the protein’s natural form | A chemist, through a deliberate covalent link |
| Typical example | Hemoglobin with heme | An antibody-drug conjugate, a PEGylated protein, or a conjugate vaccine (Holz et al., 2023) |
How protein conjugation works in practice
The reviews below describe the chemistry at the level of which part of the protein is targeted and which reagent class does the targeting. They are not protocols, and this page gives no reaction steps.
Which residues are targeted
Sornay et al. note that lysine is one of the most abundant amino acids in proteins, that cysteine residues are one of the most convenient targets in bioconjugation, and that the amino group at the protein’s N-terminus can also be modified. Holz et al. (Pharmaceutics, 2023) describe N-hydroxysuccinimide (NHS) esters reacting with solvent-exposed lysine side chains, and maleimide linkers reacting with thiols, which gives a thiosuccinimide through Michael addition. They also describe disulfide rebridging with bifunctional cysteine-reactive linkers and the use of unnatural amino acids for click chemistry.
Chemoselective versus site-selective
Sornay et al. define the two terms separately. Chemoselectivity is the selective modification of a side-chain functional group on the protein’s amino acids. Site-selectivity is the preferential conjugation of a single residue on the protein of interest. The same review notes that the vast majority of site-selective strategies still employ chemoselective reagents.
Why a “conjugate” is often a mixture
Sornay et al. report that chemoselective conjugation can give “regioisomeric mixtures of thousands of species with various degrees of conjugation”. For an IgG carrying six payloads on lysines they put the number at approximately 120 million regioisomers. When a supplier or paper gives a “degree of conjugation”, it describes an average over a population of molecules, not one defined structure.
Types and examples of protein conjugates
Every row below is taken from Holz et al. (2023) unless noted.
| Type | What is joined to the protein | Examples named in the review |
|---|---|---|
| Antibody-drug conjugates (ADCs) | Potent cytotoxic compounds joined to an antibody by chemical conjugation | Mylotarg (gemtuzumab ozogamicin), Adcetris (brentuximab vedotin), Kadcyla (trastuzumab emtansine), Enhertu (trastuzumab deruxtecan), Trodelvy (sacituzumab govitecan) |
| PEGylated proteins | Polyethylene glycol; for filgrastim, a 20 kDa PEG at the N-terminus | Adagen (pegademase bovine, listed as the first PEGylated protein, 1990), Oncaspar (pegaspargase, 1994), Neulasta (pegfilgrastim, 2002) |
| Conjugate vaccines | A polysaccharide linked to a protein carrier to elicit a T-cell-dependent response | Prevnar 13, Vaxneuvance (PCV15), Prevnar 20; Typbar TCV pairs the Vi antigen with tetanus toxoid; CRM197 has been conjugated by reductive amination |
The same review describes cleavable linkers in ADCs as reducible disulfides, acid-labile hydrazones and protease-cleavable dipeptides, which is one way the linker chemistry differs between products.
Where it matters for labs and supply decisions
Protein conjugates also reach labs as labeled reagents, such as labeled antibodies and detection conjugates. Two checks follow from the sources above. First, ask what the label is attached to and how: a conjugate made on lysines or cysteines is a population of species, so two lots with the same stated degree of conjugation are averages. Second, ask whether the label is covalently attached or held by affinity. Holz et al. describe the avidin-biotin pairing as “noncovalent, yet very high affinity”, so a streptavidin-biotin detection system is a tight complex rather than a covalent conjugate. Background on labeled reagents is in the CASRAI guides on FITC, what biotinylated means, and immunostaining. For a conjugated protein of another kind, an antibody-drug conjugate, see the mention in hydrophobic interaction chromatography. To check protein identity and size by gel, see SDS-PAGE protein gel electrophoresis.
Common misunderstandings
- A conjugated protein is not a bioconjugate. The first is a protein with a native prosthetic group; the second has been joined to a chosen molecule by chemistry.
- Binding to a protein does not make a covalent conjugate. Avidin-biotin binding is noncovalent. Prosthetic groups in the biochemistry sense may be bound tightly, and Wikipedia’s article on prosthetic groups notes that some are attached through a covalent bond while a non-covalently bound group generally cannot be removed without denaturing the protein.
- Site-selective is not the same as chemoselective. A reagent can target one kind of side chain and still modify many residues of that kind.
- “The conjugate” is rarely one molecule. Lysine-directed methods in particular give large mixtures, as the 120 million regioisomer figure shows.
FAQ
What is a conjugated protein?
A protein that has a non-amino-acid part, called a prosthetic group, such as a metal, lipid, sugar or phosphate. Hemoglobin with its heme is the standard example (LibreTexts, Brevard College).
What is a protein conjugate?
A protein covalently linked to another molecule, the product of bioconjugation (Sornay et al., 2022). Antibody-drug conjugates, PEGylated proteins and conjugate vaccines are examples (Holz et al., 2023).
Is protein conjugation the same as conjugating proteins?
Both phrases name the act of covalently linking a protein to another molecule; “protein conjugates” names the products.
Is the avidin-biotin bond a covalent conjugate?
No. Holz et al. describe it as noncovalent, yet very high affinity binding.
Sources
- Sornay C, Vaur V, Wagner A, Chaubet G. “An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteins.” Royal Society Open Science, 2022. pmc.ncbi.nlm.nih.gov/articles/PMC8790347. Checked 2026-10-29.
- Holz E, et al. “A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future.” Pharmaceutics, 2023. pmc.ncbi.nlm.nih.gov/articles/PMC9959917. Checked 2026-10-29.
- “Classification of Proteins,” Chemistry LibreTexts, CHE 301 Biochemistry, Brevard College (CC BY-NC-SA 4.0). chem.libretexts.org. Checked 2026-10-29.
- “Prosthetic group,” Wikipedia. en.wikipedia.org/wiki/Prosthetic_group. Checked 2026-10-29.
