Try with AmpliTaq Gold 360 PCR Master Mix (Cat # 4398881) by Thermo Scientific, is very effective for high GC rich PCR. I am tested it in plant sample PCR for 66% GC.

As mentioned by Shuvobrata, suppliers of DNA polymerase usually provide alternative mixes/buffers to facilitate the amplificationi of GC-rich DNA, sometimes at the cost of a somewhat decreased fidelilty. However, if amplification still fails after several trials, I suggest to order a synthetic fragment from a gene synthesis company. The cost does not exceed a few hundred of $, even for your large fragment, and if you plan to use it for expressing a recombinant protein, you can ask for optimization of the codons.

use primers with a very high annealing temperature to minimise strand reassociation and run the pcr in a final concentration of 1molar betaine to weaken the effect of the gc triple hydrogen bonding. make the annealing time very short again to minimise reassociation

Dear Danielle,

I think it will be difficult to amplify such big amplicons with high specifity.

I would try to amplify your amplicons with other primer target sequences (with 50% to 60% GC content) before and after your target sequence.

Best regards,

Thomas

Your amplicon size is too large still you can go through this protocols

https://academic.oup.com/nar/article/25/19/3957/2549226

Article DMSO and Betaine Greatly Improve Amplification of GC-Rich Co...

Hope it will help you.

You can use the Phusion® High-Fidelity DNA Polymerase with the buffer for amplicons with high GC content. Additionally, you can add DMSO at 0.5-5% to the reaction mix in order to decrease the Tm or add deionized formamide instead.

Good luck,

JA

I suggest using 5% (v/v) DMSO. You may reduce the concentration even upto 1% through optimization. It should work.

Best of luck.

Thank you everyone--what I should have included was that the fragment forms tetra-G structures. It's a 600 bp long sequence with 80 repeat of GGGG (with 4 non-G base pairs in between). Does anyone have any way of amplifying this