Bio-Synthesis offers macrocyclic metal chelator conjugation services by covalently
attached peptides, oligonucleotides, antibodies or drugs to those metal chelating
ligands that can be used as molecular imaging probes. Relying on a state-of-the
art chemical biology facilities and over 30 years of combined experience in providing
high quality chelator-biopolymer complexes, each custom project is meticulously
monitored according to Bio-Synthesis's stringent quality assurance and quality control
standard that are fully backed up by a bioanalytical laboratory. The end-products
of metal ion conjugates are used for radioimmunodetection, radioimmunotherapy, magnetic
resonance imaging, photodynamic therapy or other similar modalities.
Contact our Technical Service Center at 800.220.0627 or contact us online with your detailed project specifications, a project manager will be assigned to help
you with the design and develop an appropriate synthetic method for your specific needs.
As molecular imaging has become an indispensable tool in modern diagnostics in
biomedical research and therapeutic fields. Thus the need for highly sensitive and
specific molecular imaging probes is still unmet. In order to design diagnostic
imaging and radiotherapeutic agents, a high target/background ratio, target uptake
and rapid removal of untargeted drug is desirable. Proteins, peptide, antibodies
and their fragments are perfect candidates due to high specificity, affinity and
selectivity to the target organs.
There are several methods commonly used to label protein, peptide, and antibodies:
Types of Bifunctional chelating agents (BCAs) used to create radioimmunoconjugates:
DTPA (Diethylenetriaminepentaacetic Anhydride)
This BCA contains two amine-reactive anhydride groups. This compound reacts with
N-terminal and ϵ-amine groups of protein to form amide linkage. The anhydride rings
open to create multivalent, metal-chelating arms able to bind tightly metals in
a coordination complex. It has 8 coordination sites with metal ions (from 3 nitrogens
and 5 oxygens).
DOTA (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid)
This BCA containing 4 acetic acid carboxylate group off the 4 nitrogens of its 12
atom cyclic structure and is capable of modifying proteins and binding radioactive
metal ions in strong coordination complexes of up to eight dative bonds.
NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid)
NOTA has a smaller ring structure in comparison to DOTA and only has 3 chelating
carboxylate groups and 3 nitrogens, it has 6 coordination sites with metal ions.
TETA (1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid)
TETA has 4 chelating carboxylate group s and 4 nitrogens. C- and N-functionalized
derivatives can be prepare wit TETA. A p-bromoacetamidobenzyle-TETA derivative could
be used to label antibodies through sulfhydryl groups.
This BCA contains four carboxylate groups and 3 nitrogens that can hold metals tightly
in a coordination complex of seven dative bonds. This compound is good at chelating
lanthanide element series, such as europium, samarium, terbium and dysprosium. This
BCA is primarily used for complexing metals to form fluorescent probes for time-resolved
Sample Submission Requirement:
Biomolecules supplied by customers should be sufficiently pure. Please provide 5
mgs of starting material with the necessary data for purity assessment. Commercially
available biopolymers can be supplied by customers or synthesized or ordered through
Price varies based on the proejct specifications. Price does not includes cost of small molecule or biopolymer which required to be order through Bio-Synthesis from a commercial vendor. Some of the small molecules or biomolecules are commerically available in an activated form. For non-active molecules, Bio-Synthesis can assist with the design and, if deemed necessary, biopolymer modification to introduce additional functional groups and extra linkers, spacers. Please contact us for a quote
Discount: 15 % discount price applies to additional conjugates
ordered at the same time.
Series of metal chelating ligands can be covalently attached to biopolymer such as
oligonucleotide, antibodies, peptide and proteins. This indirect method of biolmolecule
labeling with radiolabels utilize organic compounds able to chelate metal ions in
a coordination complex. They are widely used in nuclear medicine, MRI, and optical
These bifunctional chelating ligands can be covalently attached to biopolymers such
as oligonucleotides, antibodies, peptides and proteins. They are widely used in nuclear
medicine, MRI, and optical imaging applications.
Magnetic Resonance Imaging (MRI) contrast agents are a group of contrast media used
to improve the visibility of internal body structures using MRI. We offer agents
that are being developed for the ability to measure physiological properties such
as pH and temperature.
Chemistry: Coupling of preactivated small molecule and biomolecules
with chemical reactive groups such as amine, thiol, carboxylate, hydroxyl, aldehyde
and ketone, active hydrogen through use of various cross linkers.
CAUTION: Conjugation with antibody may cause some immunogloublins to lose antigen-binding
activity after modification. Pilot experiment to optimize the amount of protein/antibody
present and the quantity of metal chelator added to the reaction needs to be done
first in order to avoid this type of corsslinking and polymerization.
Service Specification: After standard desalting, or purification,
a small percent of heterogeneous products containing single or multi-site conjugate
per molecule may exist.
Procedure: After labeling, final conjugates must first be isolated
from excess or unreacted reagent by gel filtration or dialysis. Additional
purification technique such as stirred cell filtration, tangential flow filtration
(TFF), gel filtration chromatography may also be used to either remove excess reagent
or isolate and characterized the cross-linked product. For reagents (mostly protein and other biological molecules)
that are similar in size or larger than the antibody, one must resort to other purification
techniques such as affinity chromatography, ion-exchange chromatography, and hydrophobic
Cross-linked target molecule may then be further characterized by biochemical or
biophysical techniques. Once the product has been purified, it may be subject to
many different types of studies including spectroscopic (MALDI-TOF, ESI, LC-MS Fluorescence),
electrophoresis, immunochemical biochemical, enzymatical analysis. QC (quality control)
and QA (quality assurance) procedures are also followed independently to offer you
double guarantee for the highest quality possible of every delivered conjugates.
Moreover, our dedicated technical account managers will guide your project through
every step of the process and constantly keep you informed of the latest project
Visit our literature vaults for more references and citings.
For us to better understand your customized project, please complete our Bioconjugation Service Questionnaire. The more our chemists understand your project needs, the more accurate feedback we will be able to provide you. Providing us with your project details will enable us to recommend the best reagents to use for your own project. The most useful and readily available tools for bioconjugation projects are cross-linking reagents. A large number of cross-linkers, also known as bifunctional reagents, have been developed. There are several ways to classify the cross-linkers, such as the type of reactive group, hydrophobicity or hydrophilicity, and the length of the spacer between reactive groups. Other factors to consider are whether the two reactive groups are the same or different (for example, heterobifunctional or homobifunctional reagents), whether the spacer is cleavable, and whether the reagents are membrane permeable or impermeable. The most accessible and abundant reactive groups in proteins are the ϵ-amino groups of lysine. Therefore, a large number of the most common cross-linkers are amino selective reagents, such as imidoesters, sulfo-N-hydroxysuccinimide esters, and N-hydroxysuccinimide esters. Due to the high reactivity of the thiol group with N-ethylmaleimide, iodoacetate and a-halocarbonyl compounds, new cross-linkers have been developed that contain maleimide and a-carbonyl moieties. Usually, N-alkylmaleimides are more stable than their N-aryl counterparts.
In addition to the reactive groups on the cross-linkers, a wide variety of connectors and spacer arms have also been developed. The nature of the spacer arm, and also the length, play an important role in the functionality. Longer spacer arms are generally more effective when coupling large proteins or those with sterically protected reactive side-chains. Other important considerations are the hydrophobicity, hydrophilicity, and the conformational flexibility. Long aliphatic chains generally fold on themselves when in an aqueous environment, which makes the actual distance spanned by such linker arms less than expected. Instead, spacers that contain more rigid structures (for example, aromatic groups or cycloalkanes) should be used. These structures, however, tend to be very hydrophobic which could significantly decrease the solubility of the modified molecules or even modify some of their properties. In such cases, it is recommended to choose a spacer that contains an alkylether (PEO) chain. Bio-Synthesis offers several cross-linkers with PEO chains, such as thiol-binding homobifunctional reagents, heterobifunctional based, and their derivatives.
Once the project scope has collected, we will provide an appropriate quotation within 3-5 days. Orders can be placed with either a PO (Purchase Order) or credit card. We accept POs and major credit cards ( ). Your credit card will be billed under 'Bio-Synthesis, Inc.' Click here to download our credit reference form. For international orders, we must apply the full charge at the time of the order is placed. In the unlikely event that any given order cannot be filled, our guarantee will take the form of a full refund.