Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1996-06-10
1997-09-23
Nutter, Nathan M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
530323, 530324, 530333, 528310, 528315, 528322, 528332, 528422, 528423, 528425, 526258, 548215, A61K 3700
Patent
active
056704801
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a novel method of controlled polymerization to produce encoded synthetic polymers, involving the stepwise assembly of discrete modules having selected structural features in a manner so as to produce a polymer having (1) a precisely ordered sequence of structural units; or (2) a precisely ordered sequence of structural units and a specific uniform chain length and molecular weight, depending on the particular strategy chosen; and (3) resultant physiochemical and biological properties which are the sum of the individual properties of the modules and their specific arrangement in the polymer.
BACKGROUND OF THE INVENTION
Existing polymerization methods fall into one of two basic types; (1) Addition or Chain Growth Polymerization; and (2) Condensation or Step-Growth Polymerization.
Chain growth polymerizations most commonly utilize monomers possessing reactive carbon-carbon double bonds, although other species, such as cyclic ethers , e.g., ethylene and propylene oxide and aldehydes, e.g., formaldehyde, can be polymerized in this way. These chain-growth polymerizations are characterized by the fact that the free radical, ionic or metal complex intermediates involved in the process are transient and can not be isolated. A generalized example for a simple free radical initiated vinyl polymerization is shown below: ##STR1##
Step-growth polymerizations involve reactions which occur between molecules containing multiple reactive groups which can react with each other. An example of this is the well-known reaction of a glycol and a dibasic aromatic acid to give a polyester.
It can be readily seen that the use of multiple reactive monomers possessing groups with similar or equivalent reactivities with this method produces a mixture of individual polymer species having random arrangements of monomeric sequences and only statistical control of the resulting stoichiometric make-up.
While many different variations of these two classes of polymerization reaction schemes exist, e.g. initiation may be cationic, radical, anionic, sequential aldol, ring-opening or displacement, and many different reactive species may be employed, e.g. electron deficient alkenes, epoxides, polyamines, hydroxyesters, etc., all of these variations possess a common limiting feature--they all rely on a statistical or average stoichiometric control of the final polymeric product. This is achieved through the careful selection and control of the reaction conditions, such a concentration of monomers, agitation conditions, catalyst level, time/temperature cycles, etc.. These existing polymerization methods do not have any ability to control the exact constitution or length of any specific individual polymer chain. The properties of the polymers produced via these processes are, in fact, a statistical average of the properties of a complex mixture of subtly differing individual polymer species having a range of molecular weights and containing differing combinations and sequences of monomers along the chains. Even in the simplest example of a step growth polymerization involving only two reactants, where the product is a polymer containing a single repeating structural motif, the product obtained will consist of a statistical mixture of a large number of individual molecules each having differing lengths and molecular weights.
In spite of these limitations, those skilled in the art have developed strategies by which these methods can be exploited. Average chain length can be controlled roughly by the ratio of initiator to monomer, or by quenching with an additive giving a range of molecular weights. Macroscopic properties can be modulated by the addition of comonomers which are incorporated randomly into the backbone. However, these methods possess no ability to have discreet or even reproducible microsequence control , and the "address" of a singular functionality added to the polymerization reaction is statistically determined.
Most natural biological polymers, such as oligonucleotides, prot
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ArQule, Inc.
Nutter Nathan M.
Truong Duc
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